Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14840 | 44743;44744;44745 | chr2:178625303;178625302;178625301 | chr2:179490030;179490029;179490028 |
| N2AB | 13199 | 39820;39821;39822 | chr2:178625303;178625302;178625301 | chr2:179490030;179490029;179490028 |
| N2A | 12272 | 37039;37040;37041 | chr2:178625303;178625302;178625301 | chr2:179490030;179490029;179490028 |
| N2B | 5775 | 17548;17549;17550 | chr2:178625303;178625302;178625301 | chr2:179490030;179490029;179490028 |
| Novex-1 | 5900 | 17923;17924;17925 | chr2:178625303;178625302;178625301 | chr2:179490030;179490029;179490028 |
| Novex-2 | 5967 | 18124;18125;18126 | chr2:178625303;178625302;178625301 | chr2:179490030;179490029;179490028 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs1296759910  |
-1.667 | 0.999 | N | 0.643 | 0.383 | 0.212008924253 | gnomAD-2.1.1 | 4.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.34E-05 | None | 0 | 0 | 0 |
| F/L | rs1296759910 |
-1.667 | 0.999 | N | 0.643 | 0.383 | 0.212008924253 | gnomAD-4.0.0 | 4.81645E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.34682E-05 | 0 |
| F/S | rs886055276 |
-3.418 | 1.0 | N | 0.709 | 0.452 | 0.546435761033 | gnomAD-2.1.1 | 4.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.67E-05 | None | 0 | None | 0 | 0 | 0 |
| F/S | rs886055276 |
-3.418 | 1.0 | N | 0.709 | 0.452 | 0.546435761033 | gnomAD-4.0.0 | 1.60548E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.79783E-05 | None | 0 | 0 | 0 | 0 | 0 |
| F/Y | rs886055276 |
None | 0.999 | N | 0.617 | 0.262 | 0.304760801415 | gnomAD-4.0.0 | 6.42191E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.15172E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.9051 | likely_pathogenic | 0.9405 | pathogenic | -1.747 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| F/C | 0.702 | likely_pathogenic | 0.836 | pathogenic | -0.834 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | N | 0.450411641 | None | None | N |
| F/D | 0.974 | likely_pathogenic | 0.9763 | pathogenic | -0.054 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| F/E | 0.9702 | likely_pathogenic | 0.9717 | pathogenic | 0.002 | Stabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| F/G | 0.9627 | likely_pathogenic | 0.971 | pathogenic | -2.048 | Highly Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| F/H | 0.8808 | likely_pathogenic | 0.8895 | pathogenic | -0.429 | Destabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | N |
| F/I | 0.4919 | ambiguous | 0.5894 | pathogenic | -0.877 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | N | 0.441513532 | None | None | N |
| F/K | 0.9679 | likely_pathogenic | 0.9705 | pathogenic | -0.819 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| F/L | 0.9549 | likely_pathogenic | 0.9651 | pathogenic | -0.877 | Destabilizing | 0.999 | D | 0.643 | neutral | N | 0.401729603 | None | None | N |
| F/M | 0.7714 | likely_pathogenic | 0.8196 | pathogenic | -0.687 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| F/N | 0.9367 | likely_pathogenic | 0.943 | pathogenic | -0.802 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| F/P | 0.9987 | likely_pathogenic | 0.9991 | pathogenic | -1.156 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| F/Q | 0.9411 | likely_pathogenic | 0.9472 | pathogenic | -0.831 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| F/R | 0.9306 | likely_pathogenic | 0.9361 | pathogenic | -0.275 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| F/S | 0.8768 | likely_pathogenic | 0.911 | pathogenic | -1.597 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | N | 0.420768443 | None | None | N |
| F/T | 0.8747 | likely_pathogenic | 0.9091 | pathogenic | -1.441 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| F/V | 0.4995 | ambiguous | 0.609 | pathogenic | -1.156 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | N | 0.425724291 | None | None | N |
| F/W | 0.7823 | likely_pathogenic | 0.7963 | pathogenic | -0.304 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | N |
| F/Y | 0.3558 | ambiguous | 0.3741 | ambiguous | -0.468 | Destabilizing | 0.999 | D | 0.617 | neutral | N | 0.447719041 | 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.