Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30421 | 91486;91487;91488 | chr2:178551639;178551638;178551637 | chr2:179416366;179416365;179416364 |
| N2AB | 28780 | 86563;86564;86565 | chr2:178551639;178551638;178551637 | chr2:179416366;179416365;179416364 |
| N2A | 27853 | 83782;83783;83784 | chr2:178551639;178551638;178551637 | chr2:179416366;179416365;179416364 |
| N2B | 21356 | 64291;64292;64293 | chr2:178551639;178551638;178551637 | chr2:179416366;179416365;179416364 |
| Novex-1 | 21481 | 64666;64667;64668 | chr2:178551639;178551638;178551637 | chr2:179416366;179416365;179416364 |
| Novex-2 | 21548 | 64867;64868;64869 | chr2:178551639;178551638;178551637 | chr2:179416366;179416365;179416364 |
| 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/A | None | None | 0.994 | N | 0.536 | 0.197 | 0.184867976434 | gnomAD-4.0.0 | 1.68656E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.92419E-05 | 0 | 0 | 0 | 0 |
| S/P | rs1699486002  |
None | 0.999 | N | 0.642 | 0.372 | 0.301789629655 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/P | rs1699486002 |
None | 0.999 | N | 0.642 | 0.372 | 0.301789629655 | gnomAD-4.0.0 | 6.57065E-06 | None | None | None | None | I | None | 0 | 6.54793E-05 | None | 0 | 0 | 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 | 0.1851 | likely_benign | 0.1783 | benign | -0.211 | Destabilizing | 0.994 | D | 0.536 | neutral | N | 0.41292463 | None | None | I |
| S/C | 0.2773 | likely_benign | 0.2309 | benign | -0.315 | Destabilizing | 1.0 | D | 0.729 | deleterious | N | 0.504933501 | None | None | I |
| S/D | 0.7753 | likely_pathogenic | 0.7366 | pathogenic | 0.117 | Stabilizing | 0.998 | D | 0.62 | neutral | None | None | None | None | I |
| S/E | 0.9195 | likely_pathogenic | 0.9064 | pathogenic | 0.008 | Stabilizing | 0.998 | D | 0.619 | neutral | None | None | None | None | I |
| S/F | 0.5386 | ambiguous | 0.5449 | ambiguous | -0.919 | Destabilizing | 0.999 | D | 0.702 | prob.delet. | N | 0.504933501 | None | None | I |
| S/G | 0.2712 | likely_benign | 0.2279 | benign | -0.27 | Destabilizing | 0.998 | D | 0.475 | neutral | None | None | None | None | I |
| S/H | 0.7504 | likely_pathogenic | 0.7032 | pathogenic | -0.691 | Destabilizing | 1.0 | D | 0.723 | deleterious | None | None | None | None | I |
| S/I | 0.5241 | ambiguous | 0.5257 | ambiguous | -0.191 | Destabilizing | 0.999 | D | 0.625 | neutral | None | None | None | None | I |
| S/K | 0.979 | likely_pathogenic | 0.9766 | pathogenic | -0.371 | Destabilizing | 0.998 | D | 0.613 | neutral | None | None | None | None | I |
| S/L | 0.2091 | likely_benign | 0.2202 | benign | -0.191 | Destabilizing | 0.999 | D | 0.535 | neutral | None | None | None | None | I |
| S/M | 0.4053 | ambiguous | 0.3944 | ambiguous | -0.048 | Destabilizing | 1.0 | D | 0.728 | deleterious | None | None | None | None | I |
| S/N | 0.2853 | likely_benign | 0.2402 | benign | -0.138 | Destabilizing | 0.998 | D | 0.619 | neutral | None | None | None | None | I |
| S/P | 0.5917 | likely_pathogenic | 0.6356 | pathogenic | -0.172 | Destabilizing | 0.999 | D | 0.642 | neutral | N | 0.452235167 | None | None | I |
| S/Q | 0.8724 | likely_pathogenic | 0.8534 | pathogenic | -0.383 | Destabilizing | 0.999 | D | 0.645 | neutral | None | None | None | None | I |
| S/R | 0.9719 | likely_pathogenic | 0.9688 | pathogenic | -0.145 | Destabilizing | 0.999 | D | 0.645 | neutral | None | None | None | None | I |
| S/T | 0.2005 | likely_benign | 0.1929 | benign | -0.253 | Destabilizing | 0.997 | D | 0.465 | neutral | N | 0.416794442 | None | None | I |
| S/V | 0.5176 | ambiguous | 0.5145 | ambiguous | -0.172 | Destabilizing | 0.999 | D | 0.596 | neutral | None | None | None | None | I |
| S/W | 0.7235 | likely_pathogenic | 0.731 | pathogenic | -0.972 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | I |
| S/Y | 0.5069 | ambiguous | 0.4802 | ambiguous | -0.667 | Destabilizing | 0.999 | D | 0.705 | prob.delet. | N | 0.480152487 | 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.