Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15208 | 45847;45848;45849 | chr2:178620988;178620987;178620986 | chr2:179485715;179485714;179485713 |
| N2AB | 13567 | 40924;40925;40926 | chr2:178620988;178620987;178620986 | chr2:179485715;179485714;179485713 |
| N2A | 12640 | 38143;38144;38145 | chr2:178620988;178620987;178620986 | chr2:179485715;179485714;179485713 |
| N2B | 6143 | 18652;18653;18654 | chr2:178620988;178620987;178620986 | chr2:179485715;179485714;179485713 |
| Novex-1 | 6268 | 19027;19028;19029 | chr2:178620988;178620987;178620986 | chr2:179485715;179485714;179485713 |
| Novex-2 | 6335 | 19228;19229;19230 | chr2:178620988;178620987;178620986 | chr2:179485715;179485714;179485713 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs1339878633  |
-1.626 | 0.999 | D | 0.774 | 0.398 | 0.74166409102 | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.68862E-04 |
| L/F | rs1339878633 |
-1.626 | 0.999 | D | 0.774 | 0.398 | 0.74166409102 | gnomAD-4.0.0 | 2.74473E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.70143E-06 | 0 | 1.66262E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9241 | likely_pathogenic | 0.911 | pathogenic | -1.865 | Destabilizing | 0.997 | D | 0.64 | neutral | None | None | None | None | N |
| L/C | 0.9641 | likely_pathogenic | 0.9508 | pathogenic | -0.986 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| L/D | 0.9961 | likely_pathogenic | 0.9952 | pathogenic | -1.57 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| L/E | 0.9803 | likely_pathogenic | 0.9756 | pathogenic | -1.593 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| L/F | 0.8491 | likely_pathogenic | 0.7852 | pathogenic | -1.475 | Destabilizing | 0.999 | D | 0.774 | deleterious | D | 0.559336177 | None | None | N |
| L/G | 0.9833 | likely_pathogenic | 0.9781 | pathogenic | -2.173 | Highly Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| L/H | 0.9783 | likely_pathogenic | 0.9732 | pathogenic | -1.429 | Destabilizing | 1.0 | D | 0.778 | deleterious | D | 0.561045745 | None | None | N |
| L/I | 0.4182 | ambiguous | 0.3615 | ambiguous | -1.085 | Destabilizing | 0.992 | D | 0.584 | neutral | D | 0.547634836 | None | None | N |
| L/K | 0.9721 | likely_pathogenic | 0.9675 | pathogenic | -1.286 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| L/M | 0.4015 | ambiguous | 0.3476 | ambiguous | -0.711 | Destabilizing | 0.985 | D | 0.522 | neutral | None | None | None | None | N |
| L/N | 0.9714 | likely_pathogenic | 0.963 | pathogenic | -1.009 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| L/P | 0.8264 | likely_pathogenic | 0.8629 | pathogenic | -1.315 | Destabilizing | 1.0 | D | 0.801 | deleterious | N | 0.497265979 | None | None | N |
| L/Q | 0.9414 | likely_pathogenic | 0.9288 | pathogenic | -1.26 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| L/R | 0.9604 | likely_pathogenic | 0.9562 | pathogenic | -0.609 | Destabilizing | 0.999 | D | 0.783 | deleterious | D | 0.560485558 | None | None | N |
| L/S | 0.9821 | likely_pathogenic | 0.9744 | pathogenic | -1.556 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| L/T | 0.9323 | likely_pathogenic | 0.9074 | pathogenic | -1.474 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| L/V | 0.4932 | ambiguous | 0.44 | ambiguous | -1.315 | Destabilizing | 0.992 | D | 0.575 | neutral | N | 0.497793297 | None | None | N |
| L/W | 0.9677 | likely_pathogenic | 0.9492 | pathogenic | -1.533 | Destabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | N |
| L/Y | 0.9779 | likely_pathogenic | 0.9653 | pathogenic | -1.34 | Destabilizing | 1.0 | D | 0.785 | 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.