Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6823 | 20692;20693;20694 | chr2:178725855;178725854;178725853 | chr2:179590582;179590581;179590580 |
| N2AB | 6506 | 19741;19742;19743 | chr2:178725855;178725854;178725853 | chr2:179590582;179590581;179590580 |
| N2A | 5579 | 16960;16961;16962 | chr2:178725855;178725854;178725853 | chr2:179590582;179590581;179590580 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 | None | None | 0.991 | D | 0.601 | 0.601 | 0.791347535812 | gnomAD-4.0.0 | 6.8443E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16001E-05 | 0 |
| V/G | rs529417675  |
-2.075 | 0.967 | D | 0.63 | 0.572 | 0.789912218454 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.63527E-04 | None | 0 | 0 | 0 |
| V/G | rs529417675 |
-2.075 | 0.967 | D | 0.63 | 0.572 | 0.789912218454 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06954E-04 | 0 |
| V/G | rs529417675 |
-2.075 | 0.967 | D | 0.63 | 0.572 | 0.789912218454 | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 2E-03 | None |
| V/G | rs529417675 |
-2.075 | 0.967 | D | 0.63 | 0.572 | 0.789912218454 | gnomAD-4.0.0 | 1.17767E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39126E-06 | 1.53789E-04 | 1.60133E-05 |
| V/M | None | None | 0.88 | D | 0.585 | 0.429 | 0.54173910141 | 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 | 0.2833 | likely_benign | 0.2244 | benign | -2.008 | Highly Destabilizing | 0.337 | N | 0.474 | neutral | N | 0.516975371 | None | None | N |
| V/C | 0.8468 | likely_pathogenic | 0.8039 | pathogenic | -2.203 | Highly Destabilizing | 0.993 | D | 0.601 | neutral | None | None | None | None | N |
| V/D | 0.9494 | likely_pathogenic | 0.9364 | pathogenic | -3.293 | Highly Destabilizing | 0.999 | D | 0.647 | neutral | None | None | None | None | N |
| V/E | 0.9109 | likely_pathogenic | 0.8995 | pathogenic | -3.206 | Highly Destabilizing | 0.991 | D | 0.601 | neutral | D | 0.544068743 | None | None | N |
| V/F | 0.4308 | ambiguous | 0.3976 | ambiguous | -1.471 | Destabilizing | 0.932 | D | 0.636 | neutral | None | None | None | None | N |
| V/G | 0.5924 | likely_pathogenic | 0.5073 | ambiguous | -2.398 | Highly Destabilizing | 0.967 | D | 0.63 | neutral | D | 0.532712437 | None | None | N |
| V/H | 0.9624 | likely_pathogenic | 0.9508 | pathogenic | -1.882 | Destabilizing | 0.994 | D | 0.634 | neutral | None | None | None | None | N |
| V/I | 0.0878 | likely_benign | 0.0827 | benign | -0.967 | Destabilizing | 0.008 | N | 0.484 | neutral | None | None | None | None | N |
| V/K | 0.9361 | likely_pathogenic | 0.9331 | pathogenic | -1.884 | Destabilizing | 0.997 | D | 0.607 | neutral | None | None | None | None | N |
| V/L | 0.2842 | likely_benign | 0.2624 | benign | -0.967 | Destabilizing | 0.001 | N | 0.179 | neutral | N | 0.477441122 | None | None | N |
| V/M | 0.2195 | likely_benign | 0.2043 | benign | -1.069 | Destabilizing | 0.88 | D | 0.585 | neutral | D | 0.522988747 | None | None | N |
| V/N | 0.859 | likely_pathogenic | 0.8064 | pathogenic | -2.137 | Highly Destabilizing | 0.979 | D | 0.661 | neutral | None | None | None | None | N |
| V/P | 0.8889 | likely_pathogenic | 0.8543 | pathogenic | -1.286 | Destabilizing | 0.993 | D | 0.623 | neutral | None | None | None | None | N |
| V/Q | 0.8983 | likely_pathogenic | 0.8825 | pathogenic | -2.241 | Highly Destabilizing | 0.999 | D | 0.623 | neutral | None | None | None | None | N |
| V/R | 0.9002 | likely_pathogenic | 0.9018 | pathogenic | -1.385 | Destabilizing | 0.998 | D | 0.666 | neutral | None | None | None | None | N |
| V/S | 0.5876 | likely_pathogenic | 0.4684 | ambiguous | -2.596 | Highly Destabilizing | 0.449 | N | 0.579 | neutral | None | None | None | None | N |
| V/T | 0.2803 | likely_benign | 0.2348 | benign | -2.394 | Highly Destabilizing | 0.009 | N | 0.255 | neutral | None | None | None | None | N |
| V/W | 0.9606 | likely_pathogenic | 0.956 | pathogenic | -1.83 | Destabilizing | 0.998 | D | 0.645 | neutral | None | None | None | None | N |
| V/Y | 0.9135 | likely_pathogenic | 0.8934 | pathogenic | -1.531 | Destabilizing | 0.956 | D | 0.655 | neutral | 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.