Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2138 | 6637;6638;6639 | chr2:178775452;178775451;178775450 | chr2:179640179;179640178;179640177 |
| N2AB | 2138 | 6637;6638;6639 | chr2:178775452;178775451;178775450 | chr2:179640179;179640178;179640177 |
| N2A | 2138 | 6637;6638;6639 | chr2:178775452;178775451;178775450 | chr2:179640179;179640178;179640177 |
| N2B | 2092 | 6499;6500;6501 | chr2:178775452;178775451;178775450 | chr2:179640179;179640178;179640177 |
| Novex-1 | 2092 | 6499;6500;6501 | chr2:178775452;178775451;178775450 | chr2:179640179;179640178;179640177 |
| Novex-2 | 2092 | 6499;6500;6501 | chr2:178775452;178775451;178775450 | chr2:179640179;179640178;179640177 |
| Novex-3 | 2138 | 6637;6638;6639 | chr2:178775452;178775451;178775450 | chr2:179640179;179640178;179640177 |
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/M | rs368391123  |
None | 1.0 | D | 0.76 | 0.612 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/M | rs368391123 |
None | 1.0 | D | 0.76 | 0.612 | None | gnomAD-4.0.0 | 3.04488E-06 | None | None | None | None | N | None | 5.24292E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs2092116298 |
None | 0.993 | D | 0.393 | 0.598 | 0.773490639186 | gnomAD-4.0.0 | 1.59068E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43271E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9578 | likely_pathogenic | 0.972 | pathogenic | -2.999 | Highly Destabilizing | 0.999 | D | 0.694 | prob.neutral | None | None | None | None | N |
| I/C | 0.9555 | likely_pathogenic | 0.9656 | pathogenic | -2.287 | Highly Destabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | N |
| I/D | 0.9986 | likely_pathogenic | 0.999 | pathogenic | -3.509 | Highly Destabilizing | 1.0 | D | 0.888 | deleterious | None | None | None | None | N |
| I/E | 0.9938 | likely_pathogenic | 0.9955 | pathogenic | -3.231 | Highly Destabilizing | 1.0 | D | 0.89 | deleterious | None | None | None | None | N |
| I/F | 0.3357 | likely_benign | 0.446 | ambiguous | -1.816 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| I/G | 0.9943 | likely_pathogenic | 0.9965 | pathogenic | -3.586 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| I/H | 0.982 | likely_pathogenic | 0.9881 | pathogenic | -3.039 | Highly Destabilizing | 1.0 | D | 0.882 | deleterious | None | None | None | None | N |
| I/K | 0.9858 | likely_pathogenic | 0.9899 | pathogenic | -2.492 | Highly Destabilizing | 1.0 | D | 0.889 | deleterious | D | 0.754684538 | None | None | N |
| I/L | 0.2079 | likely_benign | 0.2422 | benign | -1.26 | Destabilizing | 0.993 | D | 0.437 | neutral | D | 0.618950658 | None | None | N |
| I/M | 0.2252 | likely_benign | 0.2536 | benign | -1.276 | Destabilizing | 1.0 | D | 0.76 | deleterious | D | 0.757021101 | None | None | N |
| I/N | 0.9784 | likely_pathogenic | 0.9845 | pathogenic | -3.024 | Highly Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | None | N |
| I/P | 0.9986 | likely_pathogenic | 0.999 | pathogenic | -1.826 | Destabilizing | 1.0 | D | 0.892 | deleterious | None | None | None | None | N |
| I/Q | 0.9808 | likely_pathogenic | 0.9868 | pathogenic | -2.791 | Highly Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| I/R | 0.9764 | likely_pathogenic | 0.9837 | pathogenic | -2.224 | Highly Destabilizing | 1.0 | D | 0.891 | deleterious | D | 0.824098718 | None | None | N |
| I/S | 0.9661 | likely_pathogenic | 0.9783 | pathogenic | -3.691 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| I/T | 0.9523 | likely_pathogenic | 0.9644 | pathogenic | -3.26 | Highly Destabilizing | 1.0 | D | 0.824 | deleterious | D | 0.824322788 | None | None | N |
| I/V | 0.1467 | likely_benign | 0.1579 | benign | -1.826 | Destabilizing | 0.993 | D | 0.393 | neutral | D | 0.648948745 | None | None | N |
| I/W | 0.9622 | likely_pathogenic | 0.9761 | pathogenic | -2.241 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| I/Y | 0.8863 | likely_pathogenic | 0.9281 | pathogenic | -2.003 | Highly Destabilizing | 1.0 | D | 0.811 | 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.