Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3245 | 9958;9959;9960 | chr2:178764782;178764781;178764780 | chr2:179629509;179629508;179629507 |
| N2AB | 3245 | 9958;9959;9960 | chr2:178764782;178764781;178764780 | chr2:179629509;179629508;179629507 |
| N2A | 3245 | 9958;9959;9960 | chr2:178764782;178764781;178764780 | chr2:179629509;179629508;179629507 |
| N2B | 3199 | 9820;9821;9822 | chr2:178764782;178764781;178764780 | chr2:179629509;179629508;179629507 |
| Novex-1 | 3199 | 9820;9821;9822 | chr2:178764782;178764781;178764780 | chr2:179629509;179629508;179629507 |
| Novex-2 | 3199 | 9820;9821;9822 | chr2:178764782;178764781;178764780 | chr2:179629509;179629508;179629507 |
| Novex-3 | 3245 | 9958;9959;9960 | chr2:178764782;178764781;178764780 | chr2:179629509;179629508;179629507 |
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 | rs752456528  |
-1.893 | 0.151 | D | 0.377 | 0.404 | 0.554518586217 | gnomAD-4.0.0 | 3.18361E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71484E-06 | 0 | 0 |
| L/V | rs752456528 |
None | 0.835 | D | 0.574 | 0.371 | 0.6013344672 | 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 |
| L/V | rs752456528 |
None | 0.835 | D | 0.574 | 0.371 | 0.6013344672 | gnomAD-4.0.0 | 2.56272E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.7846E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9287 | likely_pathogenic | 0.9576 | pathogenic | -2.344 | Highly Destabilizing | 0.97 | D | 0.629 | neutral | None | None | None | None | N |
| L/C | 0.9539 | likely_pathogenic | 0.9712 | pathogenic | -1.624 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| L/D | 0.9979 | likely_pathogenic | 0.9988 | pathogenic | -2.293 | Highly Destabilizing | 0.999 | D | 0.779 | deleterious | None | None | None | None | N |
| L/E | 0.9903 | likely_pathogenic | 0.9944 | pathogenic | -2.177 | Highly Destabilizing | 0.999 | D | 0.793 | deleterious | None | None | None | None | N |
| L/F | 0.7104 | likely_pathogenic | 0.8335 | pathogenic | -1.527 | Destabilizing | 0.151 | N | 0.377 | neutral | D | 0.588454292 | None | None | N |
| L/G | 0.9845 | likely_pathogenic | 0.991 | pathogenic | -2.797 | Highly Destabilizing | 0.996 | D | 0.768 | deleterious | None | None | None | None | N |
| L/H | 0.986 | likely_pathogenic | 0.9922 | pathogenic | -2.071 | Highly Destabilizing | 1.0 | D | 0.767 | deleterious | D | 0.649950528 | None | None | N |
| L/I | 0.2434 | likely_benign | 0.3547 | ambiguous | -1.088 | Destabilizing | 0.925 | D | 0.571 | neutral | N | 0.521135158 | None | None | N |
| L/K | 0.9897 | likely_pathogenic | 0.9923 | pathogenic | -1.62 | Destabilizing | 0.996 | D | 0.711 | prob.delet. | None | None | None | None | N |
| L/M | 0.2836 | likely_benign | 0.3662 | ambiguous | -0.948 | Destabilizing | 0.559 | D | 0.376 | neutral | None | None | None | None | N |
| L/N | 0.9875 | likely_pathogenic | 0.9924 | pathogenic | -1.673 | Destabilizing | 0.999 | D | 0.783 | deleterious | None | None | None | None | N |
| L/P | 0.9145 | likely_pathogenic | 0.9478 | pathogenic | -1.482 | Destabilizing | 0.998 | D | 0.781 | deleterious | N | 0.484052081 | None | None | N |
| L/Q | 0.9703 | likely_pathogenic | 0.9839 | pathogenic | -1.733 | Destabilizing | 0.996 | D | 0.711 | prob.delet. | None | None | None | None | N |
| L/R | 0.9832 | likely_pathogenic | 0.9892 | pathogenic | -1.139 | Destabilizing | 0.994 | D | 0.726 | prob.delet. | D | 0.737708653 | None | None | N |
| L/S | 0.984 | likely_pathogenic | 0.9926 | pathogenic | -2.374 | Highly Destabilizing | 0.996 | D | 0.714 | prob.delet. | None | None | None | None | N |
| L/T | 0.9358 | likely_pathogenic | 0.9649 | pathogenic | -2.128 | Highly Destabilizing | 0.996 | D | 0.715 | prob.delet. | None | None | None | None | N |
| L/V | 0.3719 | ambiguous | 0.5035 | ambiguous | -1.482 | Destabilizing | 0.835 | D | 0.574 | neutral | D | 0.59281238 | None | None | N |
| L/W | 0.9588 | likely_pathogenic | 0.9798 | pathogenic | -1.757 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | N |
| L/Y | 0.981 | likely_pathogenic | 0.9896 | pathogenic | -1.51 | Destabilizing | 0.983 | D | 0.721 | 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.