Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24727 | 74404;74405;74406 | chr2:178571953;178571952;178571951 | chr2:179436680;179436679;179436678 |
| N2AB | 23086 | 69481;69482;69483 | chr2:178571953;178571952;178571951 | chr2:179436680;179436679;179436678 |
| N2A | 22159 | 66700;66701;66702 | chr2:178571953;178571952;178571951 | chr2:179436680;179436679;179436678 |
| N2B | 15662 | 47209;47210;47211 | chr2:178571953;178571952;178571951 | chr2:179436680;179436679;179436678 |
| Novex-1 | 15787 | 47584;47585;47586 | chr2:178571953;178571952;178571951 | chr2:179436680;179436679;179436678 |
| Novex-2 | 15854 | 47785;47786;47787 | chr2:178571953;178571952;178571951 | chr2:179436680;179436679;179436678 |
| 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/A | rs769619709  |
-1.379 | 0.999 | N | 0.475 | 0.616 | 0.767380901185 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| V/A | rs769619709 |
-1.379 | 0.999 | N | 0.475 | 0.616 | 0.767380901185 | gnomAD-4.0.0 | 3.18468E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71906E-06 | 0 | 0 |
| V/I | rs773070815 |
-0.301 | 0.997 | N | 0.445 | 0.422 | 0.825722815492 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| V/I | rs773070815 |
-0.301 | 0.997 | N | 0.445 | 0.422 | 0.825722815492 | gnomAD-4.0.0 | 6.84411E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99596E-07 | 0 | 0 |
| V/L | rs773070815 |
None | 0.997 | N | 0.49 | 0.495 | 0.755182339457 | gnomAD-4.0.0 | 2.73764E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59838E-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 | 0.484 | ambiguous | 0.5637 | ambiguous | -1.579 | Destabilizing | 0.999 | D | 0.475 | neutral | N | 0.493649409 | None | None | N |
| V/C | 0.8782 | likely_pathogenic | 0.8946 | pathogenic | -1.042 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | N |
| V/D | 0.9818 | likely_pathogenic | 0.9869 | pathogenic | -1.233 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| V/E | 0.9485 | likely_pathogenic | 0.9577 | pathogenic | -1.189 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | D | 0.553450038 | None | None | N |
| V/F | 0.706 | likely_pathogenic | 0.7566 | pathogenic | -1.104 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| V/G | 0.7484 | likely_pathogenic | 0.8118 | pathogenic | -1.948 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | D | 0.532623532 | None | None | N |
| V/H | 0.9783 | likely_pathogenic | 0.9834 | pathogenic | -1.486 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| V/I | 0.1165 | likely_benign | 0.1167 | benign | -0.644 | Destabilizing | 0.997 | D | 0.445 | neutral | N | 0.489143186 | None | None | N |
| V/K | 0.9347 | likely_pathogenic | 0.9494 | pathogenic | -1.212 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| V/L | 0.5543 | ambiguous | 0.6263 | pathogenic | -0.644 | Destabilizing | 0.997 | D | 0.49 | neutral | N | 0.497412072 | None | None | N |
| V/M | 0.4757 | ambiguous | 0.5259 | ambiguous | -0.521 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| V/N | 0.9342 | likely_pathogenic | 0.9475 | pathogenic | -1.058 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| V/P | 0.9882 | likely_pathogenic | 0.9902 | pathogenic | -0.921 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| V/Q | 0.9172 | likely_pathogenic | 0.931 | pathogenic | -1.16 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| V/R | 0.9053 | likely_pathogenic | 0.9271 | pathogenic | -0.797 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| V/S | 0.7561 | likely_pathogenic | 0.7997 | pathogenic | -1.673 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| V/T | 0.617 | likely_pathogenic | 0.6755 | pathogenic | -1.511 | Destabilizing | 0.999 | D | 0.616 | neutral | None | None | None | None | N |
| V/W | 0.9948 | likely_pathogenic | 0.9961 | pathogenic | -1.339 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | N |
| V/Y | 0.96 | likely_pathogenic | 0.97 | pathogenic | -1.024 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | 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.