Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21259 | 64000;64001;64002 | chr2:178587534;178587533;178587532 | chr2:179452261;179452260;179452259 |
| N2AB | 19618 | 59077;59078;59079 | chr2:178587534;178587533;178587532 | chr2:179452261;179452260;179452259 |
| N2A | 18691 | 56296;56297;56298 | chr2:178587534;178587533;178587532 | chr2:179452261;179452260;179452259 |
| N2B | 12194 | 36805;36806;36807 | chr2:178587534;178587533;178587532 | chr2:179452261;179452260;179452259 |
| Novex-1 | 12319 | 37180;37181;37182 | chr2:178587534;178587533;178587532 | chr2:179452261;179452260;179452259 |
| Novex-2 | 12386 | 37381;37382;37383 | chr2:178587534;178587533;178587532 | chr2:179452261;179452260;179452259 |
| 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/I | rs371286595  |
-0.073 | 0.999 | N | 0.626 | 0.299 | None | gnomAD-2.1.1 | 8.34E-05 | None | None | None | None | N | None | 4.17537E-04 | 0 | None | 0 | 0 | None | 3.34E-05 | None | 8.09E-05 | 7.93E-05 | 0 |
| V/I | rs371286595 |
-0.073 | 0.999 | N | 0.626 | 0.299 | None | gnomAD-3.1.2 | 1.11866E-04 | None | None | None | None | N | None | 4.10787E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs371286595 |
-0.073 | 0.999 | N | 0.626 | 0.299 | None | gnomAD-4.0.0 | 3.17018E-05 | None | None | None | None | N | None | 2.94645E-04 | 0 | None | 0 | 0 | None | 3.13706E-05 | 0 | 1.86892E-05 | 4.41852E-05 | 1.60705E-05 |
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 | 0.7597 | likely_pathogenic | 0.7891 | pathogenic | -1.901 | Destabilizing | 0.999 | D | 0.605 | neutral | N | 0.481752309 | None | None | N |
| V/C | 0.8273 | likely_pathogenic | 0.8495 | pathogenic | -1.559 | Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| V/D | 0.994 | likely_pathogenic | 0.9944 | pathogenic | -2.232 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| V/E | 0.9843 | likely_pathogenic | 0.9857 | pathogenic | -2.004 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | D | 0.533554449 | None | None | N |
| V/F | 0.6982 | likely_pathogenic | 0.716 | pathogenic | -1.116 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| V/G | 0.8707 | likely_pathogenic | 0.8797 | pathogenic | -2.462 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | D | 0.526971084 | None | None | N |
| V/H | 0.9893 | likely_pathogenic | 0.9914 | pathogenic | -2.274 | Highly Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| V/I | 0.1081 | likely_benign | 0.114 | benign | -0.341 | Destabilizing | 0.999 | D | 0.626 | neutral | N | 0.466546551 | None | None | N |
| V/K | 0.9844 | likely_pathogenic | 0.9861 | pathogenic | -1.555 | Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| V/L | 0.5332 | ambiguous | 0.5741 | pathogenic | -0.341 | Destabilizing | 0.999 | D | 0.613 | neutral | D | 0.532768756 | None | None | N |
| V/M | 0.5896 | likely_pathogenic | 0.6269 | pathogenic | -0.473 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| V/N | 0.9745 | likely_pathogenic | 0.979 | pathogenic | -1.868 | Destabilizing | 1.0 | D | 0.885 | deleterious | None | None | None | None | N |
| V/P | 0.9889 | likely_pathogenic | 0.9898 | pathogenic | -0.832 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| V/Q | 0.9668 | likely_pathogenic | 0.9701 | pathogenic | -1.67 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| V/R | 0.9668 | likely_pathogenic | 0.9674 | pathogenic | -1.496 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| V/S | 0.9002 | likely_pathogenic | 0.9176 | pathogenic | -2.544 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| V/T | 0.7922 | likely_pathogenic | 0.8218 | pathogenic | -2.155 | Highly Destabilizing | 0.999 | D | 0.647 | neutral | None | None | None | None | N |
| V/W | 0.9901 | likely_pathogenic | 0.992 | pathogenic | -1.616 | Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| V/Y | 0.9676 | likely_pathogenic | 0.9722 | pathogenic | -1.2 | Destabilizing | 1.0 | D | 0.874 | deleterious | 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.