Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2160 | 6703;6704;6705 | chr2:178775386;178775385;178775384 | chr2:179640113;179640112;179640111 |
| N2AB | 2160 | 6703;6704;6705 | chr2:178775386;178775385;178775384 | chr2:179640113;179640112;179640111 |
| N2A | 2160 | 6703;6704;6705 | chr2:178775386;178775385;178775384 | chr2:179640113;179640112;179640111 |
| N2B | 2114 | 6565;6566;6567 | chr2:178775386;178775385;178775384 | chr2:179640113;179640112;179640111 |
| Novex-1 | 2114 | 6565;6566;6567 | chr2:178775386;178775385;178775384 | chr2:179640113;179640112;179640111 |
| Novex-2 | 2114 | 6565;6566;6567 | chr2:178775386;178775385;178775384 | chr2:179640113;179640112;179640111 |
| Novex-3 | 2160 | 6703;6704;6705 | chr2:178775386;178775385;178775384 | chr2:179640113;179640112;179640111 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs397517693  |
-0.888 | 0.061 | N | 0.149 | 0.111 | None | gnomAD-2.1.1 | 3.54E-05 | None | None | None | None | I | None | 0 | 1.12975E-04 | None | 0 | 0 | None | 0 | None | 0 | 4.66E-05 | 0 |
| T/A | rs397517693 |
-0.888 | 0.061 | N | 0.149 | 0.111 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 2.42E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| T/A | rs397517693 |
-0.888 | 0.061 | N | 0.149 | 0.111 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| T/A | rs397517693 |
-0.888 | 0.061 | N | 0.149 | 0.111 | None | gnomAD-4.0.0 | 4.02744E-05 | None | None | None | None | I | None | 2.66773E-05 | 8.33472E-05 | None | 0 | 0 | None | 1.56299E-05 | 0 | 4.66108E-05 | 0 | 3.1999E-05 |
| T/I | rs750401975 |
0.01 | 0.988 | N | 0.533 | 0.434 | 0.442567846599 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | I | None | 6.15E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs750401975 |
0.01 | 0.988 | N | 0.533 | 0.434 | 0.442567846599 | gnomAD-4.0.0 | 2.05229E-06 | None | None | None | None | I | None | 2.98757E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79859E-06 | 0 | 0 |
| T/N | None | None | 0.92 | N | 0.499 | 0.373 | 0.414539908741 | gnomAD-4.0.0 | 6.84097E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99295E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1268 | likely_benign | 0.1227 | benign | -0.846 | Destabilizing | 0.061 | N | 0.149 | neutral | N | 0.395946917 | None | None | I |
| T/C | 0.6643 | likely_pathogenic | 0.6499 | pathogenic | -0.587 | Destabilizing | 0.999 | D | 0.551 | neutral | None | None | None | None | I |
| T/D | 0.84 | likely_pathogenic | 0.8544 | pathogenic | -0.036 | Destabilizing | 0.939 | D | 0.509 | neutral | None | None | None | None | I |
| T/E | 0.8089 | likely_pathogenic | 0.8083 | pathogenic | -0.036 | Destabilizing | 0.939 | D | 0.522 | neutral | None | None | None | None | I |
| T/F | 0.7556 | likely_pathogenic | 0.7596 | pathogenic | -0.892 | Destabilizing | 0.997 | D | 0.667 | neutral | None | None | None | None | I |
| T/G | 0.5426 | ambiguous | 0.5719 | pathogenic | -1.1 | Destabilizing | 0.759 | D | 0.559 | neutral | None | None | None | None | I |
| T/H | 0.7709 | likely_pathogenic | 0.7685 | pathogenic | -1.292 | Destabilizing | 0.999 | D | 0.641 | neutral | None | None | None | None | I |
| T/I | 0.548 | ambiguous | 0.5216 | ambiguous | -0.263 | Destabilizing | 0.988 | D | 0.533 | neutral | N | 0.492331555 | None | None | I |
| T/K | 0.7851 | likely_pathogenic | 0.7861 | pathogenic | -0.704 | Destabilizing | 0.939 | D | 0.522 | neutral | None | None | None | None | I |
| T/L | 0.4353 | ambiguous | 0.4248 | ambiguous | -0.263 | Destabilizing | 0.939 | D | 0.475 | neutral | None | None | None | None | I |
| T/M | 0.2114 | likely_benign | 0.196 | benign | -0.073 | Destabilizing | 0.999 | D | 0.559 | neutral | None | None | None | None | I |
| T/N | 0.3585 | ambiguous | 0.368 | ambiguous | -0.623 | Destabilizing | 0.92 | D | 0.499 | neutral | N | 0.503322992 | None | None | I |
| T/P | 0.9465 | likely_pathogenic | 0.9547 | pathogenic | -0.425 | Destabilizing | 0.988 | D | 0.539 | neutral | D | 0.621340265 | None | None | I |
| T/Q | 0.6916 | likely_pathogenic | 0.6829 | pathogenic | -0.784 | Destabilizing | 0.991 | D | 0.571 | neutral | None | None | None | None | I |
| T/R | 0.7388 | likely_pathogenic | 0.7426 | pathogenic | -0.458 | Destabilizing | 0.991 | D | 0.542 | neutral | None | None | None | None | I |
| T/S | 0.2339 | likely_benign | 0.2337 | benign | -0.949 | Destabilizing | 0.31 | N | 0.208 | neutral | N | 0.498648088 | None | None | I |
| T/V | 0.3386 | likely_benign | 0.3243 | benign | -0.425 | Destabilizing | 0.939 | D | 0.433 | neutral | None | None | None | None | I |
| T/W | 0.96 | likely_pathogenic | 0.965 | pathogenic | -0.791 | Destabilizing | 0.999 | D | 0.708 | prob.delet. | None | None | None | None | I |
| T/Y | 0.8071 | likely_pathogenic | 0.8109 | pathogenic | -0.57 | Destabilizing | 0.997 | D | 0.668 | neutral | 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.