Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21404 | 64435;64436;64437 | chr2:178586691;178586690;178586689 | chr2:179451418;179451417;179451416 |
| N2AB | 19763 | 59512;59513;59514 | chr2:178586691;178586690;178586689 | chr2:179451418;179451417;179451416 |
| N2A | 18836 | 56731;56732;56733 | chr2:178586691;178586690;178586689 | chr2:179451418;179451417;179451416 |
| N2B | 12339 | 37240;37241;37242 | chr2:178586691;178586690;178586689 | chr2:179451418;179451417;179451416 |
| Novex-1 | 12464 | 37615;37616;37617 | chr2:178586691;178586690;178586689 | chr2:179451418;179451417;179451416 |
| Novex-2 | 12531 | 37816;37817;37818 | chr2:178586691;178586690;178586689 | chr2:179451418;179451417;179451416 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/R | rs1159259078  |
-0.37 | 0.976 | N | 0.747 | 0.271 | 0.245101548738 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65673E-04 |
| S/R | rs1159259078 |
-0.37 | 0.976 | N | 0.747 | 0.271 | 0.245101548738 | gnomAD-4.0.0 | 1.59262E-06 | None | None | None | None | N | None | 0 | 2.2876E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/T | None | None | 0.959 | N | 0.646 | 0.15 | 0.278143212241 | gnomAD-4.0.0 | 1.59264E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77886E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1078 | likely_benign | 0.1192 | benign | -1.138 | Destabilizing | 0.863 | D | 0.565 | neutral | None | None | None | None | N |
| S/C | 0.1466 | likely_benign | 0.1358 | benign | -0.451 | Destabilizing | 0.999 | D | 0.674 | neutral | N | 0.495047369 | None | None | N |
| S/D | 0.7711 | likely_pathogenic | 0.7473 | pathogenic | -1.552 | Destabilizing | 0.02 | N | 0.341 | neutral | None | None | None | None | N |
| S/E | 0.7489 | likely_pathogenic | 0.7504 | pathogenic | -1.295 | Destabilizing | 0.079 | N | 0.345 | neutral | None | None | None | None | N |
| S/F | 0.3824 | ambiguous | 0.3705 | ambiguous | -0.811 | Destabilizing | 0.997 | D | 0.695 | prob.neutral | None | None | None | None | N |
| S/G | 0.1942 | likely_benign | 0.2003 | benign | -1.537 | Destabilizing | 0.906 | D | 0.637 | neutral | N | 0.465244537 | None | None | N |
| S/H | 0.5566 | ambiguous | 0.5418 | ambiguous | -1.542 | Destabilizing | 0.997 | D | 0.694 | prob.neutral | None | None | None | None | N |
| S/I | 0.5064 | ambiguous | 0.4788 | ambiguous | -0.081 | Destabilizing | 0.996 | D | 0.712 | prob.delet. | N | 0.456662339 | None | None | N |
| S/K | 0.959 | likely_pathogenic | 0.9536 | pathogenic | 0.13 | Stabilizing | 0.939 | D | 0.656 | neutral | None | None | None | None | N |
| S/L | 0.3031 | likely_benign | 0.2863 | benign | -0.081 | Destabilizing | 0.969 | D | 0.72 | prob.delet. | None | None | None | None | N |
| S/M | 0.3671 | ambiguous | 0.3694 | ambiguous | -0.423 | Destabilizing | 0.999 | D | 0.672 | neutral | None | None | None | None | N |
| S/N | 0.4185 | ambiguous | 0.4028 | ambiguous | -0.639 | Destabilizing | 0.92 | D | 0.664 | neutral | N | 0.429881169 | None | None | N |
| S/P | 0.9934 | likely_pathogenic | 0.9923 | pathogenic | -0.405 | Destabilizing | 0.997 | D | 0.739 | prob.delet. | None | None | None | None | N |
| S/Q | 0.6842 | likely_pathogenic | 0.6967 | pathogenic | -0.291 | Destabilizing | 0.939 | D | 0.719 | prob.delet. | None | None | None | None | N |
| S/R | 0.9262 | likely_pathogenic | 0.9149 | pathogenic | -0.38 | Destabilizing | 0.976 | D | 0.747 | deleterious | N | 0.401211701 | None | None | N |
| S/T | 0.1584 | likely_benign | 0.1542 | benign | -0.295 | Destabilizing | 0.959 | D | 0.646 | neutral | N | 0.419104028 | None | None | N |
| S/V | 0.3929 | ambiguous | 0.3767 | ambiguous | -0.405 | Destabilizing | 0.969 | D | 0.709 | prob.delet. | None | None | None | None | N |
| S/W | 0.5085 | ambiguous | 0.4957 | ambiguous | -1.073 | Destabilizing | 0.999 | D | 0.723 | prob.delet. | None | None | None | None | N |
| S/Y | 0.3143 | likely_benign | 0.2868 | benign | -0.621 | Destabilizing | 0.997 | D | 0.694 | prob.neutral | 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.