Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24315 | 73168;73169;73170 | chr2:178573189;178573188;178573187 | chr2:179437916;179437915;179437914 |
| N2AB | 22674 | 68245;68246;68247 | chr2:178573189;178573188;178573187 | chr2:179437916;179437915;179437914 |
| N2A | 21747 | 65464;65465;65466 | chr2:178573189;178573188;178573187 | chr2:179437916;179437915;179437914 |
| N2B | 15250 | 45973;45974;45975 | chr2:178573189;178573188;178573187 | chr2:179437916;179437915;179437914 |
| Novex-1 | 15375 | 46348;46349;46350 | chr2:178573189;178573188;178573187 | chr2:179437916;179437915;179437914 |
| Novex-2 | 15442 | 46549;46550;46551 | chr2:178573189;178573188;178573187 | chr2:179437916;179437915;179437914 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/H | rs794729492  |
-0.646 | 0.998 | N | 0.666 | 0.382 | 0.43046518545 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.99E-06 | 0 |
| Y/H | rs794729492 |
-0.646 | 0.998 | N | 0.666 | 0.382 | 0.43046518545 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| Y/H | rs794729492 |
-0.646 | 0.998 | N | 0.666 | 0.382 | 0.43046518545 | gnomAD-4.0.0 | 2.48403E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.3963E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.476 | ambiguous | 0.4051 | ambiguous | -2.304 | Highly Destabilizing | 0.981 | D | 0.629 | neutral | None | None | None | None | N |
| Y/C | 0.0991 | likely_benign | 0.0788 | benign | -1.243 | Destabilizing | 0.999 | D | 0.781 | deleterious | N | 0.48368246 | None | None | N |
| Y/D | 0.6614 | likely_pathogenic | 0.5509 | ambiguous | -1.911 | Destabilizing | 0.998 | D | 0.773 | deleterious | N | 0.48368246 | None | None | N |
| Y/E | 0.7541 | likely_pathogenic | 0.6686 | pathogenic | -1.757 | Destabilizing | 0.998 | D | 0.771 | deleterious | None | None | None | None | N |
| Y/F | 0.079 | likely_benign | 0.0856 | benign | -0.812 | Destabilizing | 0.058 | N | 0.306 | neutral | N | 0.471401102 | None | None | N |
| Y/G | 0.5836 | likely_pathogenic | 0.4838 | ambiguous | -2.662 | Highly Destabilizing | 0.995 | D | 0.748 | deleterious | None | None | None | None | N |
| Y/H | 0.1799 | likely_benign | 0.1525 | benign | -1.088 | Destabilizing | 0.998 | D | 0.666 | prob.neutral | N | 0.465324716 | None | None | N |
| Y/I | 0.3162 | likely_benign | 0.2572 | benign | -1.167 | Destabilizing | 0.979 | D | 0.69 | prob.delet. | None | None | None | None | N |
| Y/K | 0.6759 | likely_pathogenic | 0.5892 | pathogenic | -1.671 | Destabilizing | 0.998 | D | 0.775 | deleterious | None | None | None | None | N |
| Y/L | 0.4234 | ambiguous | 0.3482 | ambiguous | -1.167 | Destabilizing | 0.929 | D | 0.589 | neutral | None | None | None | None | N |
| Y/M | 0.5419 | ambiguous | 0.4833 | ambiguous | -0.887 | Destabilizing | 0.999 | D | 0.712 | prob.delet. | None | None | None | None | N |
| Y/N | 0.4006 | ambiguous | 0.2851 | benign | -2.333 | Highly Destabilizing | 0.998 | D | 0.784 | deleterious | N | 0.471908081 | None | None | N |
| Y/P | 0.9432 | likely_pathogenic | 0.9215 | pathogenic | -1.55 | Destabilizing | 0.998 | D | 0.763 | deleterious | None | None | None | None | N |
| Y/Q | 0.4316 | ambiguous | 0.3505 | ambiguous | -2.124 | Highly Destabilizing | 0.998 | D | 0.739 | deleterious | None | None | None | None | N |
| Y/R | 0.449 | ambiguous | 0.3777 | ambiguous | -1.404 | Destabilizing | 0.998 | D | 0.785 | deleterious | None | None | None | None | N |
| Y/S | 0.2515 | likely_benign | 0.1778 | benign | -2.743 | Highly Destabilizing | 0.993 | D | 0.755 | deleterious | N | 0.470894123 | None | None | N |
| Y/T | 0.3855 | ambiguous | 0.307 | benign | -2.481 | Highly Destabilizing | 0.995 | D | 0.763 | deleterious | None | None | None | None | N |
| Y/V | 0.2541 | likely_benign | 0.207 | benign | -1.55 | Destabilizing | 0.963 | D | 0.699 | prob.delet. | None | None | None | None | N |
| Y/W | 0.3812 | ambiguous | 0.377 | ambiguous | -0.317 | Destabilizing | 1.0 | D | 0.645 | neutral | 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.