Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31275 | 94048;94049;94050 | chr2:178547803;178547802;178547801 | chr2:179412530;179412529;179412528 |
| N2AB | 29634 | 89125;89126;89127 | chr2:178547803;178547802;178547801 | chr2:179412530;179412529;179412528 |
| N2A | 28707 | 86344;86345;86346 | chr2:178547803;178547802;178547801 | chr2:179412530;179412529;179412528 |
| N2B | 22210 | 66853;66854;66855 | chr2:178547803;178547802;178547801 | chr2:179412530;179412529;179412528 |
| Novex-1 | 22335 | 67228;67229;67230 | chr2:178547803;178547802;178547801 | chr2:179412530;179412529;179412528 |
| Novex-2 | 22402 | 67429;67430;67431 | chr2:178547803;178547802;178547801 | chr2:179412530;179412529;179412528 |
| 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 | None | None | 0.002 | N | 0.375 | 0.397 | 0.506734346222 | gnomAD-4.0.0 | 1.59111E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88246E-05 | 0 | 0 | 0 | 0 |
| V/I | rs1287511397  |
-0.659 | 0.002 | N | 0.343 | 0.058 | 0.165133752707 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| V/I | rs1287511397 |
-0.659 | 0.002 | N | 0.343 | 0.058 | 0.165133752707 | gnomAD-4.0.0 | 1.59114E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85789E-06 | 0 | 0 |
| V/L | None | None | 0.034 | N | 0.611 | 0.103 | 0.256793551483 | gnomAD-4.0.0 | 1.59114E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85789E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.6051 | likely_pathogenic | 0.6357 | pathogenic | -2.21 | Highly Destabilizing | 0.002 | N | 0.375 | neutral | N | 0.506447292 | None | None | N |
| V/C | 0.8215 | likely_pathogenic | 0.8476 | pathogenic | -2.092 | Highly Destabilizing | 0.947 | D | 0.736 | prob.delet. | None | None | None | None | N |
| V/D | 0.9657 | likely_pathogenic | 0.9753 | pathogenic | -2.863 | Highly Destabilizing | 0.826 | D | 0.851 | deleterious | None | None | None | None | N |
| V/E | 0.902 | likely_pathogenic | 0.9239 | pathogenic | -2.647 | Highly Destabilizing | 0.638 | D | 0.84 | deleterious | N | 0.507207761 | None | None | N |
| V/F | 0.4778 | ambiguous | 0.5463 | ambiguous | -1.358 | Destabilizing | 0.7 | D | 0.749 | deleterious | None | None | None | None | N |
| V/G | 0.6992 | likely_pathogenic | 0.7603 | pathogenic | -2.742 | Highly Destabilizing | 0.468 | N | 0.826 | deleterious | N | 0.507207761 | None | None | N |
| V/H | 0.9334 | likely_pathogenic | 0.9525 | pathogenic | -2.431 | Highly Destabilizing | 0.982 | D | 0.825 | deleterious | None | None | None | None | N |
| V/I | 0.097 | likely_benign | 0.0969 | benign | -0.727 | Destabilizing | 0.002 | N | 0.343 | neutral | N | 0.370173931 | None | None | N |
| V/K | 0.8539 | likely_pathogenic | 0.8932 | pathogenic | -1.827 | Destabilizing | 0.7 | D | 0.84 | deleterious | None | None | None | None | N |
| V/L | 0.3308 | likely_benign | 0.3625 | ambiguous | -0.727 | Destabilizing | 0.034 | N | 0.611 | neutral | N | 0.494615799 | None | None | N |
| V/M | 0.2828 | likely_benign | 0.3474 | ambiguous | -0.989 | Destabilizing | 0.7 | D | 0.683 | prob.neutral | None | None | None | None | N |
| V/N | 0.8861 | likely_pathogenic | 0.914 | pathogenic | -2.197 | Highly Destabilizing | 0.826 | D | 0.853 | deleterious | None | None | None | None | N |
| V/P | 0.9766 | likely_pathogenic | 0.9793 | pathogenic | -1.195 | Destabilizing | 0.826 | D | 0.839 | deleterious | None | None | None | None | N |
| V/Q | 0.8363 | likely_pathogenic | 0.8788 | pathogenic | -2.05 | Highly Destabilizing | 0.826 | D | 0.843 | deleterious | None | None | None | None | N |
| V/R | 0.8092 | likely_pathogenic | 0.8511 | pathogenic | -1.642 | Destabilizing | 0.826 | D | 0.842 | deleterious | None | None | None | None | N |
| V/S | 0.7632 | likely_pathogenic | 0.8071 | pathogenic | -2.833 | Highly Destabilizing | 0.539 | D | 0.827 | deleterious | None | None | None | None | N |
| V/T | 0.691 | likely_pathogenic | 0.732 | pathogenic | -2.47 | Highly Destabilizing | 0.399 | N | 0.667 | neutral | None | None | None | None | N |
| V/W | 0.9612 | likely_pathogenic | 0.9704 | pathogenic | -1.828 | Destabilizing | 0.982 | D | 0.815 | deleterious | None | None | None | None | N |
| V/Y | 0.8767 | likely_pathogenic | 0.9038 | pathogenic | -1.481 | Destabilizing | 0.826 | D | 0.741 | deleterious | 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.