Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15036 | 45331;45332;45333 | chr2:178621718;178621717;178621716 | chr2:179486445;179486444;179486443 |
| N2AB | 13395 | 40408;40409;40410 | chr2:178621718;178621717;178621716 | chr2:179486445;179486444;179486443 |
| N2A | 12468 | 37627;37628;37629 | chr2:178621718;178621717;178621716 | chr2:179486445;179486444;179486443 |
| N2B | 5971 | 18136;18137;18138 | chr2:178621718;178621717;178621716 | chr2:179486445;179486444;179486443 |
| Novex-1 | 6096 | 18511;18512;18513 | chr2:178621718;178621717;178621716 | chr2:179486445;179486444;179486443 |
| Novex-2 | 6163 | 18712;18713;18714 | chr2:178621718;178621717;178621716 | chr2:179486445;179486444;179486443 |
| 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/S | rs1256583434  |
0.14 | 0.999 | N | 0.559 | 0.326 | 0.335661160332 | gnomAD-2.1.1 | 4.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.29E-05 | None | 0 | 0 | 0 |
| N/S | rs1256583434 |
0.14 | 0.999 | N | 0.559 | 0.326 | 0.335661160332 | gnomAD-4.0.0 | 3.19258E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.87332E-05 | 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 | 0.3308 | likely_benign | 0.3505 | ambiguous | -0.823 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| N/C | 0.6094 | likely_pathogenic | 0.5753 | pathogenic | 0.159 | Stabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| N/D | 0.2203 | likely_benign | 0.2048 | benign | 0.149 | Stabilizing | 0.999 | D | 0.6 | neutral | N | 0.485533172 | None | None | N |
| N/E | 0.47 | ambiguous | 0.4919 | ambiguous | 0.178 | Stabilizing | 0.999 | D | 0.675 | prob.neutral | None | None | None | None | N |
| N/F | 0.7138 | likely_pathogenic | 0.7046 | pathogenic | -0.811 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| N/G | 0.3751 | ambiguous | 0.3899 | ambiguous | -1.089 | Destabilizing | 0.999 | D | 0.577 | neutral | None | None | None | None | N |
| N/H | 0.1657 | likely_benign | 0.1611 | benign | -0.862 | Destabilizing | 1.0 | D | 0.661 | neutral | N | 0.510168819 | None | None | N |
| N/I | 0.3481 | ambiguous | 0.3356 | benign | -0.178 | Destabilizing | 1.0 | D | 0.817 | deleterious | N | 0.493181393 | None | None | N |
| N/K | 0.2999 | likely_benign | 0.317 | benign | -0.042 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | N | 0.45519415 | None | None | N |
| N/L | 0.3707 | ambiguous | 0.3975 | ambiguous | -0.178 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| N/M | 0.4496 | ambiguous | 0.4619 | ambiguous | 0.258 | Stabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| N/P | 0.3095 | likely_benign | 0.4035 | ambiguous | -0.365 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| N/Q | 0.3932 | ambiguous | 0.4149 | ambiguous | -0.531 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| N/R | 0.415 | ambiguous | 0.4231 | ambiguous | 0.003 | Stabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| N/S | 0.1414 | likely_benign | 0.1388 | benign | -0.507 | Destabilizing | 0.999 | D | 0.559 | neutral | N | 0.501206356 | None | None | N |
| N/T | 0.2032 | likely_benign | 0.2034 | benign | -0.295 | Destabilizing | 0.999 | D | 0.667 | neutral | N | 0.493483324 | None | None | N |
| N/V | 0.3775 | ambiguous | 0.3796 | ambiguous | -0.365 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| N/W | 0.8875 | likely_pathogenic | 0.8847 | pathogenic | -0.585 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| N/Y | 0.2318 | likely_benign | 0.219 | benign | -0.404 | Destabilizing | 1.0 | D | 0.777 | deleterious | D | 0.549141635 | 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.