Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31456 | 94591;94592;94593 | chr2:178547159;178547158;178547157 | chr2:179411886;179411885;179411884 |
| N2AB | 29815 | 89668;89669;89670 | chr2:178547159;178547158;178547157 | chr2:179411886;179411885;179411884 |
| N2A | 28888 | 86887;86888;86889 | chr2:178547159;178547158;178547157 | chr2:179411886;179411885;179411884 |
| N2B | 22391 | 67396;67397;67398 | chr2:178547159;178547158;178547157 | chr2:179411886;179411885;179411884 |
| Novex-1 | 22516 | 67771;67772;67773 | chr2:178547159;178547158;178547157 | chr2:179411886;179411885;179411884 |
| Novex-2 | 22583 | 67972;67973;67974 | chr2:178547159;178547158;178547157 | chr2:179411886;179411885;179411884 |
| 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/M | rs1559156264  |
None | 0.983 | N | 0.527 | 0.27 | 0.571728244252 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| V/M | rs1559156264 |
None | 0.983 | N | 0.527 | 0.27 | 0.571728244252 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs1559156264 |
None | 0.983 | N | 0.527 | 0.27 | 0.571728244252 | gnomAD-4.0.0 | 2.56218E-06 | None | None | None | None | I | None | 1.6913E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.393E-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 | 0.3102 | likely_benign | 0.2731 | benign | -1.039 | Destabilizing | 0.008 | N | 0.193 | neutral | N | 0.491409631 | None | None | I |
| V/C | 0.7708 | likely_pathogenic | 0.7351 | pathogenic | -0.766 | Destabilizing | 0.989 | D | 0.575 | neutral | None | None | None | None | I |
| V/D | 0.6504 | likely_pathogenic | 0.6614 | pathogenic | -0.747 | Destabilizing | 0.961 | D | 0.662 | neutral | None | None | None | None | I |
| V/E | 0.4072 | ambiguous | 0.4166 | ambiguous | -0.783 | Destabilizing | 0.901 | D | 0.567 | neutral | N | 0.493084499 | None | None | I |
| V/F | 0.2905 | likely_benign | 0.2996 | benign | -0.8 | Destabilizing | 0.961 | D | 0.545 | neutral | None | None | None | None | I |
| V/G | 0.3387 | likely_benign | 0.3096 | benign | -1.293 | Destabilizing | 0.565 | D | 0.535 | neutral | N | 0.475358484 | None | None | I |
| V/H | 0.6959 | likely_pathogenic | 0.6781 | pathogenic | -0.722 | Destabilizing | 0.996 | D | 0.667 | neutral | None | None | None | None | I |
| V/I | 0.0853 | likely_benign | 0.0858 | benign | -0.472 | Destabilizing | 0.775 | D | 0.499 | neutral | None | None | None | None | I |
| V/K | 0.5215 | ambiguous | 0.5321 | ambiguous | -0.958 | Destabilizing | 0.923 | D | 0.577 | neutral | None | None | None | None | I |
| V/L | 0.2349 | likely_benign | 0.2349 | benign | -0.472 | Destabilizing | 0.349 | N | 0.513 | neutral | N | 0.500471831 | None | None | I |
| V/M | 0.1466 | likely_benign | 0.1375 | benign | -0.444 | Destabilizing | 0.983 | D | 0.527 | neutral | N | 0.470439713 | None | None | I |
| V/N | 0.347 | ambiguous | 0.324 | benign | -0.743 | Destabilizing | 0.961 | D | 0.661 | neutral | None | None | None | None | I |
| V/P | 0.9818 | likely_pathogenic | 0.9777 | pathogenic | -0.625 | Destabilizing | 0.961 | D | 0.621 | neutral | None | None | None | None | I |
| V/Q | 0.3334 | likely_benign | 0.3165 | benign | -0.928 | Destabilizing | 0.961 | D | 0.617 | neutral | None | None | None | None | I |
| V/R | 0.5219 | ambiguous | 0.5271 | ambiguous | -0.396 | Destabilizing | 0.923 | D | 0.655 | neutral | None | None | None | None | I |
| V/S | 0.3188 | likely_benign | 0.2797 | benign | -1.205 | Destabilizing | 0.633 | D | 0.502 | neutral | None | None | None | None | I |
| V/T | 0.252 | likely_benign | 0.205 | benign | -1.136 | Destabilizing | 0.044 | N | 0.238 | neutral | None | None | None | None | I |
| V/W | 0.9164 | likely_pathogenic | 0.9137 | pathogenic | -0.938 | Destabilizing | 0.996 | D | 0.674 | neutral | None | None | None | None | I |
| V/Y | 0.6889 | likely_pathogenic | 0.6943 | pathogenic | -0.661 | Destabilizing | 0.987 | D | 0.551 | 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.