Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20130 | 60613;60614;60615 | chr2:178591337;178591336;178591335 | chr2:179456064;179456063;179456062 |
| N2AB | 18489 | 55690;55691;55692 | chr2:178591337;178591336;178591335 | chr2:179456064;179456063;179456062 |
| N2A | 17562 | 52909;52910;52911 | chr2:178591337;178591336;178591335 | chr2:179456064;179456063;179456062 |
| N2B | 11065 | 33418;33419;33420 | chr2:178591337;178591336;178591335 | chr2:179456064;179456063;179456062 |
| Novex-1 | 11190 | 33793;33794;33795 | chr2:178591337;178591336;178591335 | chr2:179456064;179456063;179456062 |
| Novex-2 | 11257 | 33994;33995;33996 | chr2:178591337;178591336;178591335 | chr2:179456064;179456063;179456062 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs2050148296  |
None | 0.999 | N | 0.395 | 0.303 | 0.385906861911 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/E | rs2050148296 |
None | 0.999 | N | 0.395 | 0.303 | 0.385906861911 | gnomAD-4.0.0 | 6.57696E-06 | None | None | None | None | N | None | 0 | 6.55652E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/H | rs772986855 |
-0.473 | 1.0 | N | 0.649 | 0.425 | 0.455173453901 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/H | rs772986855 |
-0.473 | 1.0 | N | 0.649 | 0.425 | 0.455173453901 | gnomAD-4.0.0 | 3.18439E-06 | None | None | None | None | N | None | 0 | 4.57352E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2747 | likely_benign | 0.2981 | benign | -0.532 | Destabilizing | 0.996 | D | 0.575 | neutral | N | 0.476704829 | None | None | N |
| D/C | 0.785 | likely_pathogenic | 0.8025 | pathogenic | -0.029 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| D/E | 0.2814 | likely_benign | 0.3017 | benign | -0.297 | Destabilizing | 0.999 | D | 0.395 | neutral | N | 0.442744184 | None | None | N |
| D/F | 0.8011 | likely_pathogenic | 0.8259 | pathogenic | -0.384 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| D/G | 0.1925 | likely_benign | 0.2014 | benign | -0.727 | Destabilizing | 0.999 | D | 0.619 | neutral | N | 0.480534568 | None | None | N |
| D/H | 0.4936 | ambiguous | 0.5032 | ambiguous | -0.221 | Destabilizing | 1.0 | D | 0.649 | neutral | N | 0.487404758 | None | None | N |
| D/I | 0.6574 | likely_pathogenic | 0.6828 | pathogenic | -0.058 | Destabilizing | 0.998 | D | 0.685 | prob.neutral | None | None | None | None | N |
| D/K | 0.5817 | likely_pathogenic | 0.6032 | pathogenic | 0.295 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| D/L | 0.6168 | likely_pathogenic | 0.6278 | pathogenic | -0.058 | Destabilizing | 0.998 | D | 0.667 | neutral | None | None | None | None | N |
| D/M | 0.7938 | likely_pathogenic | 0.8035 | pathogenic | 0.186 | Stabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| D/N | 0.1115 | likely_benign | 0.1099 | benign | -0.126 | Destabilizing | 1.0 | D | 0.608 | neutral | N | 0.504736792 | None | None | N |
| D/P | 0.9386 | likely_pathogenic | 0.9275 | pathogenic | -0.196 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | N |
| D/Q | 0.5355 | ambiguous | 0.5552 | ambiguous | -0.073 | Destabilizing | 1.0 | D | 0.625 | neutral | None | None | None | None | N |
| D/R | 0.626 | likely_pathogenic | 0.6413 | pathogenic | 0.44 | Stabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| D/S | 0.1458 | likely_benign | 0.1506 | benign | -0.209 | Destabilizing | 1.0 | D | 0.591 | neutral | None | None | None | None | N |
| D/T | 0.2972 | likely_benign | 0.3065 | benign | -0.042 | Destabilizing | 0.999 | D | 0.661 | neutral | None | None | None | None | N |
| D/V | 0.4148 | ambiguous | 0.4456 | ambiguous | -0.196 | Destabilizing | 0.884 | D | 0.425 | neutral | N | 0.510817403 | None | None | N |
| D/W | 0.9576 | likely_pathogenic | 0.9575 | pathogenic | -0.185 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| D/Y | 0.4697 | ambiguous | 0.4831 | ambiguous | -0.136 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | D | 0.526133572 | 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.