Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26467 | 79624;79625;79626 | chr2:178566733;178566732;178566731 | chr2:179431460;179431459;179431458 |
| N2AB | 24826 | 74701;74702;74703 | chr2:178566733;178566732;178566731 | chr2:179431460;179431459;179431458 |
| N2A | 23899 | 71920;71921;71922 | chr2:178566733;178566732;178566731 | chr2:179431460;179431459;179431458 |
| N2B | 17402 | 52429;52430;52431 | chr2:178566733;178566732;178566731 | chr2:179431460;179431459;179431458 |
| Novex-1 | 17527 | 52804;52805;52806 | chr2:178566733;178566732;178566731 | chr2:179431460;179431459;179431458 |
| Novex-2 | 17594 | 53005;53006;53007 | chr2:178566733;178566732;178566731 | chr2:179431460;179431459;179431458 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | rs773008593  |
-0.319 | 0.979 | N | 0.635 | 0.247 | 0.292423486923 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.30762E-04 | None | 0 | 0 | 0 |
| A/S | rs773008593 |
-0.319 | 0.979 | N | 0.635 | 0.247 | 0.292423486923 | gnomAD-4.0.0 | 8.8968E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.50725E-04 | 0 |
| A/T | None | None | 0.958 | N | 0.739 | 0.35 | 0.322230723748 | gnomAD-4.0.0 | 2.05311E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.47826E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6782 | likely_pathogenic | 0.7143 | pathogenic | -0.861 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | I |
| A/D | 0.9846 | likely_pathogenic | 0.9846 | pathogenic | -0.653 | Destabilizing | 0.998 | D | 0.839 | deleterious | N | 0.506033585 | None | None | I |
| A/E | 0.9448 | likely_pathogenic | 0.9506 | pathogenic | -0.81 | Destabilizing | 0.995 | D | 0.791 | deleterious | None | None | None | None | I |
| A/F | 0.7378 | likely_pathogenic | 0.7833 | pathogenic | -0.936 | Destabilizing | 0.991 | D | 0.862 | deleterious | None | None | None | None | I |
| A/G | 0.4551 | ambiguous | 0.4478 | ambiguous | -0.354 | Destabilizing | 0.979 | D | 0.643 | neutral | N | 0.480901438 | None | None | I |
| A/H | 0.9486 | likely_pathogenic | 0.9535 | pathogenic | -0.284 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | I |
| A/I | 0.6094 | likely_pathogenic | 0.645 | pathogenic | -0.432 | Destabilizing | 0.938 | D | 0.713 | prob.delet. | None | None | None | None | I |
| A/K | 0.9802 | likely_pathogenic | 0.9807 | pathogenic | -0.71 | Destabilizing | 0.995 | D | 0.791 | deleterious | None | None | None | None | I |
| A/L | 0.6487 | likely_pathogenic | 0.6705 | pathogenic | -0.432 | Destabilizing | 0.938 | D | 0.579 | neutral | None | None | None | None | I |
| A/M | 0.6493 | likely_pathogenic | 0.6986 | pathogenic | -0.517 | Destabilizing | 0.999 | D | 0.803 | deleterious | None | None | None | None | I |
| A/N | 0.9183 | likely_pathogenic | 0.9243 | pathogenic | -0.416 | Destabilizing | 0.998 | D | 0.859 | deleterious | None | None | None | None | I |
| A/P | 0.9804 | likely_pathogenic | 0.9787 | pathogenic | -0.365 | Destabilizing | 0.998 | D | 0.797 | deleterious | D | 0.542041512 | None | None | I |
| A/Q | 0.9095 | likely_pathogenic | 0.9211 | pathogenic | -0.715 | Destabilizing | 0.998 | D | 0.811 | deleterious | None | None | None | None | I |
| A/R | 0.9371 | likely_pathogenic | 0.9357 | pathogenic | -0.181 | Destabilizing | 0.995 | D | 0.812 | deleterious | None | None | None | None | I |
| A/S | 0.2655 | likely_benign | 0.2782 | benign | -0.595 | Destabilizing | 0.979 | D | 0.635 | neutral | N | 0.473054306 | None | None | I |
| A/T | 0.5445 | ambiguous | 0.5819 | pathogenic | -0.677 | Destabilizing | 0.958 | D | 0.739 | prob.delet. | N | 0.488689799 | None | None | I |
| A/V | 0.3264 | likely_benign | 0.3485 | ambiguous | -0.365 | Destabilizing | 0.142 | N | 0.45 | neutral | N | 0.502087984 | None | None | I |
| A/W | 0.9773 | likely_pathogenic | 0.98 | pathogenic | -1.043 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | I |
| A/Y | 0.918 | likely_pathogenic | 0.9268 | pathogenic | -0.721 | Destabilizing | 0.995 | D | 0.864 | deleterious | None | None | None | None | I |
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.