Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35131 | 105616;105617;105618 | chr2:178531224;178531223;178531222 | chr2:179395951;179395950;179395949 |
| N2AB | 33490 | 100693;100694;100695 | chr2:178531224;178531223;178531222 | chr2:179395951;179395950;179395949 |
| N2A | 32563 | 97912;97913;97914 | chr2:178531224;178531223;178531222 | chr2:179395951;179395950;179395949 |
| N2B | 26066 | 78421;78422;78423 | chr2:178531224;178531223;178531222 | chr2:179395951;179395950;179395949 |
| Novex-1 | 26191 | 78796;78797;78798 | chr2:178531224;178531223;178531222 | chr2:179395951;179395950;179395949 |
| Novex-2 | 26258 | 78997;78998;78999 | chr2:178531224;178531223;178531222 | chr2:179395951;179395950;179395949 |
| 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 | None | None | 0.997 | N | 0.873 | 0.7 | 0.879508288144 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.75482E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs779464128  |
-1.315 | 0.58 | D | 0.475 | 0.26 | 0.493695379898 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.55E-05 | 0 |
| I/V | rs779464128 |
-1.315 | 0.58 | D | 0.475 | 0.26 | 0.493695379898 | 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 |
| I/V | rs779464128 |
-1.315 | 0.58 | D | 0.475 | 0.26 | 0.493695379898 | gnomAD-4.0.0 | 3.46993E-05 | None | None | None | None | N | None | 1.33483E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49197E-05 | 0 | 3.20174E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9747 | likely_pathogenic | 0.9819 | pathogenic | -2.27 | Highly Destabilizing | 0.953 | D | 0.719 | prob.delet. | None | None | None | None | N |
| I/C | 0.9802 | likely_pathogenic | 0.9802 | pathogenic | -1.555 | Destabilizing | 0.999 | D | 0.749 | deleterious | None | None | None | None | N |
| I/D | 0.9967 | likely_pathogenic | 0.9983 | pathogenic | -2.413 | Highly Destabilizing | 0.998 | D | 0.877 | deleterious | None | None | None | None | N |
| I/E | 0.9927 | likely_pathogenic | 0.9963 | pathogenic | -2.338 | Highly Destabilizing | 0.998 | D | 0.868 | deleterious | None | None | None | None | N |
| I/F | 0.4895 | ambiguous | 0.4726 | ambiguous | -1.502 | Destabilizing | 0.982 | D | 0.729 | prob.delet. | N | 0.467850485 | None | None | N |
| I/G | 0.9936 | likely_pathogenic | 0.9954 | pathogenic | -2.673 | Highly Destabilizing | 0.998 | D | 0.872 | deleterious | None | None | None | None | N |
| I/H | 0.9784 | likely_pathogenic | 0.9872 | pathogenic | -1.934 | Destabilizing | 0.999 | D | 0.857 | deleterious | None | None | None | None | N |
| I/K | 0.9726 | likely_pathogenic | 0.9863 | pathogenic | -1.621 | Destabilizing | 0.993 | D | 0.871 | deleterious | None | None | None | None | N |
| I/L | 0.2601 | likely_benign | 0.2756 | benign | -1.169 | Destabilizing | 0.02 | N | 0.256 | neutral | D | 0.525192209 | None | None | N |
| I/M | 0.2987 | likely_benign | 0.3437 | ambiguous | -1.013 | Destabilizing | 0.982 | D | 0.695 | prob.neutral | N | 0.509248903 | None | None | N |
| I/N | 0.9455 | likely_pathogenic | 0.9675 | pathogenic | -1.604 | Destabilizing | 0.997 | D | 0.873 | deleterious | N | 0.521872656 | None | None | N |
| I/P | 0.9885 | likely_pathogenic | 0.991 | pathogenic | -1.511 | Destabilizing | 0.998 | D | 0.867 | deleterious | None | None | None | None | N |
| I/Q | 0.9767 | likely_pathogenic | 0.9877 | pathogenic | -1.732 | Destabilizing | 0.998 | D | 0.875 | deleterious | None | None | None | None | N |
| I/R | 0.966 | likely_pathogenic | 0.9812 | pathogenic | -1.07 | Destabilizing | 0.993 | D | 0.865 | deleterious | None | None | None | None | N |
| I/S | 0.9653 | likely_pathogenic | 0.9791 | pathogenic | -2.222 | Highly Destabilizing | 0.991 | D | 0.848 | deleterious | N | 0.521619167 | None | None | N |
| I/T | 0.9735 | likely_pathogenic | 0.982 | pathogenic | -2.031 | Highly Destabilizing | 0.991 | D | 0.798 | deleterious | D | 0.532886567 | None | None | N |
| I/V | 0.3167 | likely_benign | 0.2951 | benign | -1.511 | Destabilizing | 0.58 | D | 0.475 | neutral | D | 0.523594699 | None | None | N |
| I/W | 0.969 | likely_pathogenic | 0.9758 | pathogenic | -1.704 | Destabilizing | 0.999 | D | 0.851 | deleterious | None | None | None | None | N |
| I/Y | 0.8885 | likely_pathogenic | 0.9107 | pathogenic | -1.483 | Destabilizing | 0.998 | D | 0.757 | 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.