Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27286 | 82081;82082;82083 | chr2:178564276;178564275;178564274 | chr2:179429003;179429002;179429001 |
| N2AB | 25645 | 77158;77159;77160 | chr2:178564276;178564275;178564274 | chr2:179429003;179429002;179429001 |
| N2A | 24718 | 74377;74378;74379 | chr2:178564276;178564275;178564274 | chr2:179429003;179429002;179429001 |
| N2B | 18221 | 54886;54887;54888 | chr2:178564276;178564275;178564274 | chr2:179429003;179429002;179429001 |
| Novex-1 | 18346 | 55261;55262;55263 | chr2:178564276;178564275;178564274 | chr2:179429003;179429002;179429001 |
| Novex-2 | 18413 | 55462;55463;55464 | chr2:178564276;178564275;178564274 | chr2:179429003;179429002;179429001 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1704824668  |
None | 0.055 | N | 0.59 | 0.265 | 0.529813890454 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/A | rs1704824668 |
None | 0.055 | N | 0.59 | 0.265 | 0.529813890454 | gnomAD-4.0.0 | 3.04491E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.61484E-06 | 0 | 0 |
| V/I | rs372784067 |
0.018 | 0.002 | N | 0.167 | 0.081 | None | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | I | None | 1.93849E-04 | 2.9E-05 | None | 0 | 0 | None | 9.8E-05 | None | 0 | 0 | 0 |
| V/I | rs372784067 |
0.018 | 0.002 | N | 0.167 | 0.081 | None | gnomAD-3.1.2 | 1.05168E-04 | None | None | None | None | I | None | 3.86007E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs372784067 |
0.018 | 0.002 | N | 0.167 | 0.081 | None | gnomAD-4.0.0 | 2.60347E-05 | None | None | None | None | I | None | 3.73752E-04 | 3.33389E-05 | None | 0 | 0 | None | 0 | 0 | 4.23807E-06 | 6.58747E-05 | 1.60113E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2142 | likely_benign | 0.1912 | benign | -1.258 | Destabilizing | 0.055 | N | 0.59 | neutral | N | 0.484909542 | None | None | I |
| V/C | 0.7505 | likely_pathogenic | 0.7423 | pathogenic | -0.711 | Destabilizing | 0.909 | D | 0.653 | neutral | None | None | None | None | I |
| V/D | 0.5638 | ambiguous | 0.5349 | ambiguous | -1.329 | Destabilizing | 0.497 | N | 0.739 | prob.delet. | N | 0.490874251 | None | None | I |
| V/E | 0.401 | ambiguous | 0.3936 | ambiguous | -1.328 | Destabilizing | 0.567 | D | 0.702 | prob.neutral | None | None | None | None | I |
| V/F | 0.2313 | likely_benign | 0.2052 | benign | -0.963 | Destabilizing | 0.715 | D | 0.663 | neutral | N | 0.518386255 | None | None | I |
| V/G | 0.3943 | ambiguous | 0.3927 | ambiguous | -1.548 | Destabilizing | 0.497 | N | 0.735 | prob.delet. | D | 0.529235582 | None | None | I |
| V/H | 0.6357 | likely_pathogenic | 0.61 | pathogenic | -1.089 | Destabilizing | 0.968 | D | 0.741 | deleterious | None | None | None | None | I |
| V/I | 0.075 | likely_benign | 0.0702 | benign | -0.565 | Destabilizing | 0.002 | N | 0.167 | neutral | N | 0.471704441 | None | None | I |
| V/K | 0.4693 | ambiguous | 0.4718 | ambiguous | -1.226 | Destabilizing | 0.567 | D | 0.7 | prob.neutral | None | None | None | None | I |
| V/L | 0.1883 | likely_benign | 0.1794 | benign | -0.565 | Destabilizing | 0.048 | N | 0.405 | neutral | N | 0.492773582 | None | None | I |
| V/M | 0.1453 | likely_benign | 0.1348 | benign | -0.427 | Destabilizing | 0.567 | D | 0.545 | neutral | None | None | None | None | I |
| V/N | 0.3828 | ambiguous | 0.3225 | benign | -1.02 | Destabilizing | 0.567 | D | 0.749 | deleterious | None | None | None | None | I |
| V/P | 0.698 | likely_pathogenic | 0.6541 | pathogenic | -0.762 | Destabilizing | 0.726 | D | 0.717 | prob.delet. | None | None | None | None | I |
| V/Q | 0.4065 | ambiguous | 0.4121 | ambiguous | -1.176 | Destabilizing | 0.726 | D | 0.721 | prob.delet. | None | None | None | None | I |
| V/R | 0.4047 | ambiguous | 0.4066 | ambiguous | -0.676 | Destabilizing | 0.567 | D | 0.747 | deleterious | None | None | None | None | I |
| V/S | 0.2656 | likely_benign | 0.2361 | benign | -1.426 | Destabilizing | 0.396 | N | 0.649 | neutral | None | None | None | None | I |
| V/T | 0.1433 | likely_benign | 0.1071 | benign | -1.326 | Destabilizing | 0.003 | N | 0.277 | neutral | None | None | None | None | I |
| V/W | 0.8413 | likely_pathogenic | 0.8309 | pathogenic | -1.197 | Destabilizing | 0.968 | D | 0.711 | prob.delet. | None | None | None | None | I |
| V/Y | 0.6136 | likely_pathogenic | 0.5984 | pathogenic | -0.898 | Destabilizing | 0.726 | D | 0.677 | prob.neutral | None | None | 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.