Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25857 | 77794;77795;77796 | chr2:178568563;178568562;178568561 | chr2:179433290;179433289;179433288 |
| N2AB | 24216 | 72871;72872;72873 | chr2:178568563;178568562;178568561 | chr2:179433290;179433289;179433288 |
| N2A | 23289 | 70090;70091;70092 | chr2:178568563;178568562;178568561 | chr2:179433290;179433289;179433288 |
| N2B | 16792 | 50599;50600;50601 | chr2:178568563;178568562;178568561 | chr2:179433290;179433289;179433288 |
| Novex-1 | 16917 | 50974;50975;50976 | chr2:178568563;178568562;178568561 | chr2:179433290;179433289;179433288 |
| Novex-2 | 16984 | 51175;51176;51177 | chr2:178568563;178568562;178568561 | chr2:179433290;179433289;179433288 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/N | rs781755787  |
-2.663 | 0.997 | D | 0.867 | 0.794 | 0.935398395153 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.11495E-04 | None | 0 | None | 0 | 0 | 0 |
| I/N | rs781755787 |
-2.663 | 0.997 | D | 0.867 | 0.794 | 0.935398395153 | gnomAD-4.0.0 | 1.36867E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.04185E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | None | None | 0.991 | D | 0.771 | 0.797 | 0.870264459797 | gnomAD-4.0.0 | 6.84333E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.1595E-05 | 0 |
| I/V | rs878865219 |
None | 0.58 | D | 0.4 | 0.466 | None | gnomAD-4.0.0 | 4.10596E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39764E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9218 | likely_pathogenic | 0.9333 | pathogenic | -2.866 | Highly Destabilizing | 0.953 | D | 0.697 | prob.neutral | None | None | None | None | N |
| I/C | 0.902 | likely_pathogenic | 0.9176 | pathogenic | -2.676 | Highly Destabilizing | 0.999 | D | 0.763 | deleterious | None | None | None | None | N |
| I/D | 0.9971 | likely_pathogenic | 0.9983 | pathogenic | -3.184 | Highly Destabilizing | 0.998 | D | 0.865 | deleterious | None | None | None | None | N |
| I/E | 0.9915 | likely_pathogenic | 0.9942 | pathogenic | -3.007 | Highly Destabilizing | 0.998 | D | 0.868 | deleterious | None | None | None | None | N |
| I/F | 0.3685 | ambiguous | 0.426 | ambiguous | -1.864 | Destabilizing | 0.982 | D | 0.739 | prob.delet. | D | 0.579918282 | None | None | N |
| I/G | 0.9875 | likely_pathogenic | 0.9909 | pathogenic | -3.369 | Highly Destabilizing | 0.998 | D | 0.87 | deleterious | None | None | None | None | N |
| I/H | 0.9759 | likely_pathogenic | 0.9851 | pathogenic | -2.558 | Highly Destabilizing | 0.999 | D | 0.843 | deleterious | None | None | None | None | N |
| I/K | 0.9771 | likely_pathogenic | 0.9858 | pathogenic | -2.31 | Highly Destabilizing | 0.993 | D | 0.867 | deleterious | None | None | None | None | N |
| I/L | 0.1381 | likely_benign | 0.1758 | benign | -1.427 | Destabilizing | 0.02 | N | 0.275 | neutral | D | 0.556692893 | None | None | N |
| I/M | 0.1742 | likely_benign | 0.2081 | benign | -1.567 | Destabilizing | 0.982 | D | 0.71 | prob.delet. | D | 0.606910103 | None | None | N |
| I/N | 0.9598 | likely_pathogenic | 0.9736 | pathogenic | -2.607 | Highly Destabilizing | 0.997 | D | 0.867 | deleterious | D | 0.65661298 | None | None | N |
| I/P | 0.9957 | likely_pathogenic | 0.997 | pathogenic | -1.887 | Destabilizing | 0.998 | D | 0.863 | deleterious | None | None | None | None | N |
| I/Q | 0.9735 | likely_pathogenic | 0.983 | pathogenic | -2.585 | Highly Destabilizing | 0.998 | D | 0.875 | deleterious | None | None | None | None | N |
| I/R | 0.9632 | likely_pathogenic | 0.976 | pathogenic | -1.813 | Destabilizing | 0.993 | D | 0.859 | deleterious | None | None | None | None | N |
| I/S | 0.9487 | likely_pathogenic | 0.9617 | pathogenic | -3.351 | Highly Destabilizing | 0.991 | D | 0.839 | deleterious | D | 0.65661298 | None | None | N |
| I/T | 0.9394 | likely_pathogenic | 0.9496 | pathogenic | -3.029 | Highly Destabilizing | 0.991 | D | 0.771 | deleterious | D | 0.656209372 | None | None | N |
| I/V | 0.1095 | likely_benign | 0.104 | benign | -1.887 | Destabilizing | 0.58 | D | 0.4 | neutral | D | 0.5649901 | None | None | N |
| I/W | 0.9543 | likely_pathogenic | 0.9697 | pathogenic | -2.101 | Highly Destabilizing | 0.999 | D | 0.837 | deleterious | None | None | None | None | N |
| I/Y | 0.8948 | likely_pathogenic | 0.9311 | pathogenic | -1.903 | Destabilizing | 0.993 | D | 0.765 | 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.