Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14126 | 42601;42602;42603 | chr2:178634405;178634404;178634403 | chr2:179499132;179499131;179499130 |
| N2AB | 12485 | 37678;37679;37680 | chr2:178634405;178634404;178634403 | chr2:179499132;179499131;179499130 |
| N2A | 11558 | 34897;34898;34899 | chr2:178634405;178634404;178634403 | chr2:179499132;179499131;179499130 |
| N2B | 5061 | 15406;15407;15408 | chr2:178634405;178634404;178634403 | chr2:179499132;179499131;179499130 |
| Novex-1 | 5186 | 15781;15782;15783 | chr2:178634405;178634404;178634403 | chr2:179499132;179499131;179499130 |
| Novex-2 | 5253 | 15982;15983;15984 | chr2:178634405;178634404;178634403 | chr2:179499132;179499131;179499130 |
| 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/E | rs1489018462  |
None | 1.0 | D | 0.862 | 0.702 | 0.86425461656 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/E | rs1489018462 |
None | 1.0 | D | 0.862 | 0.702 | 0.86425461656 | gnomAD-4.0.0 | 1.2414E-05 | None | None | None | None | N | None | 1.33894E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.52665E-05 | 0 | 1.60462E-05 |
| V/M | None | None | 1.0 | D | 0.783 | 0.575 | 0.510758216515 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 | 0.368 | ambiguous | 0.3513 | ambiguous | -1.801 | Destabilizing | 0.999 | D | 0.615 | neutral | N | 0.468396156 | None | None | N |
| V/C | 0.9316 | likely_pathogenic | 0.9078 | pathogenic | -1.295 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| V/D | 0.9551 | likely_pathogenic | 0.9324 | pathogenic | -1.863 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| V/E | 0.9296 | likely_pathogenic | 0.8976 | pathogenic | -1.702 | Destabilizing | 1.0 | D | 0.862 | deleterious | D | 0.675570031 | None | None | N |
| V/F | 0.6945 | likely_pathogenic | 0.6045 | pathogenic | -1.017 | Destabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | N |
| V/G | 0.6194 | likely_pathogenic | 0.5925 | pathogenic | -2.295 | Highly Destabilizing | 1.0 | D | 0.855 | deleterious | D | 0.524941839 | None | None | N |
| V/H | 0.9797 | likely_pathogenic | 0.9616 | pathogenic | -1.93 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| V/I | 0.1574 | likely_benign | 0.1482 | benign | -0.462 | Destabilizing | 0.998 | D | 0.545 | neutral | None | None | None | None | N |
| V/K | 0.9468 | likely_pathogenic | 0.9087 | pathogenic | -1.526 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| V/L | 0.7217 | likely_pathogenic | 0.67 | pathogenic | -0.462 | Destabilizing | 0.997 | D | 0.641 | neutral | D | 0.553113427 | None | None | N |
| V/M | 0.6079 | likely_pathogenic | 0.421 | ambiguous | -0.464 | Destabilizing | 1.0 | D | 0.783 | deleterious | D | 0.596056016 | None | None | N |
| V/N | 0.9068 | likely_pathogenic | 0.8605 | pathogenic | -1.628 | Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | N |
| V/P | 0.9871 | likely_pathogenic | 0.9847 | pathogenic | -0.877 | Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | N |
| V/Q | 0.9408 | likely_pathogenic | 0.8935 | pathogenic | -1.549 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| V/R | 0.9237 | likely_pathogenic | 0.8768 | pathogenic | -1.287 | Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| V/S | 0.7042 | likely_pathogenic | 0.6336 | pathogenic | -2.284 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| V/T | 0.422 | ambiguous | 0.3918 | ambiguous | -1.983 | Destabilizing | 0.999 | D | 0.623 | neutral | None | None | None | None | N |
| V/W | 0.9892 | likely_pathogenic | 0.9798 | pathogenic | -1.431 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| V/Y | 0.9412 | likely_pathogenic | 0.9092 | pathogenic | -1.055 | Destabilizing | 1.0 | D | 0.843 | 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.