Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15649 | 47170;47171;47172 | chr2:178618605;178618604;178618603 | chr2:179483332;179483331;179483330 |
| N2AB | 14008 | 42247;42248;42249 | chr2:178618605;178618604;178618603 | chr2:179483332;179483331;179483330 |
| N2A | 13081 | 39466;39467;39468 | chr2:178618605;178618604;178618603 | chr2:179483332;179483331;179483330 |
| N2B | 6584 | 19975;19976;19977 | chr2:178618605;178618604;178618603 | chr2:179483332;179483331;179483330 |
| Novex-1 | 6709 | 20350;20351;20352 | chr2:178618605;178618604;178618603 | chr2:179483332;179483331;179483330 |
| Novex-2 | 6776 | 20551;20552;20553 | chr2:178618605;178618604;178618603 | chr2:179483332;179483331;179483330 |
| 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 | rs563370509  |
-0.725 | 0.896 | N | 0.612 | 0.228 | 0.651024515444 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14705E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| F/L | rs563370509 |
-0.725 | 0.896 | N | 0.612 | 0.228 | 0.651024515444 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| F/L | rs563370509 |
-0.725 | 0.896 | N | 0.612 | 0.228 | 0.651024515444 | gnomAD-4.0.0 | 4.34229E-06 | None | None | None | None | N | None | 9.35029E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.4336 | ambiguous | 0.5061 | ambiguous | -2.276 | Highly Destabilizing | 0.919 | D | 0.717 | prob.delet. | None | None | None | None | N |
| F/C | 0.2471 | likely_benign | 0.3031 | benign | -0.904 | Destabilizing | 0.999 | D | 0.789 | deleterious | N | 0.507158356 | None | None | N |
| F/D | 0.6087 | likely_pathogenic | 0.6838 | pathogenic | -1.055 | Destabilizing | 0.976 | D | 0.777 | deleterious | None | None | None | None | N |
| F/E | 0.6633 | likely_pathogenic | 0.7049 | pathogenic | -1.01 | Destabilizing | 0.976 | D | 0.731 | prob.delet. | None | None | None | None | N |
| F/G | 0.6841 | likely_pathogenic | 0.7513 | pathogenic | -2.582 | Highly Destabilizing | 0.976 | D | 0.729 | prob.delet. | None | None | None | None | N |
| F/H | 0.3341 | likely_benign | 0.382 | ambiguous | -0.884 | Destabilizing | 0.076 | N | 0.439 | neutral | None | None | None | None | N |
| F/I | 0.1368 | likely_benign | 0.1754 | benign | -1.37 | Destabilizing | 0.984 | D | 0.621 | neutral | N | 0.505331878 | None | None | N |
| F/K | 0.7011 | likely_pathogenic | 0.7407 | pathogenic | -1.076 | Destabilizing | 0.976 | D | 0.771 | deleterious | None | None | None | None | N |
| F/L | 0.7129 | likely_pathogenic | 0.7998 | pathogenic | -1.37 | Destabilizing | 0.896 | D | 0.612 | neutral | N | 0.506222558 | None | None | N |
| F/M | 0.3729 | ambiguous | 0.4392 | ambiguous | -0.921 | Destabilizing | 0.999 | D | 0.627 | neutral | None | None | None | None | N |
| F/N | 0.3416 | ambiguous | 0.3955 | ambiguous | -0.984 | Destabilizing | 0.976 | D | 0.777 | deleterious | None | None | None | None | N |
| F/P | 0.9514 | likely_pathogenic | 0.975 | pathogenic | -1.664 | Destabilizing | 0.996 | D | 0.78 | deleterious | None | None | None | None | N |
| F/Q | 0.6141 | likely_pathogenic | 0.6546 | pathogenic | -1.166 | Destabilizing | 0.976 | D | 0.777 | deleterious | None | None | None | None | N |
| F/R | 0.6264 | likely_pathogenic | 0.6742 | pathogenic | -0.308 | Destabilizing | 0.976 | D | 0.776 | deleterious | None | None | None | None | N |
| F/S | 0.2679 | likely_benign | 0.3341 | benign | -1.741 | Destabilizing | 0.968 | D | 0.725 | prob.delet. | N | 0.497038915 | None | None | N |
| F/T | 0.3233 | likely_benign | 0.3803 | ambiguous | -1.609 | Destabilizing | 0.988 | D | 0.727 | prob.delet. | None | None | None | None | N |
| F/V | 0.1617 | likely_benign | 0.2008 | benign | -1.664 | Destabilizing | 0.896 | D | 0.692 | prob.neutral | N | 0.505331878 | None | None | N |
| F/W | 0.3989 | ambiguous | 0.4532 | ambiguous | -0.67 | Destabilizing | 0.999 | D | 0.628 | neutral | None | None | None | None | N |
| F/Y | 0.1148 | likely_benign | 0.129 | benign | -0.827 | Destabilizing | 0.103 | N | 0.315 | neutral | N | 0.50695778 | 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.