Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18805 | 56638;56639;56640 | chr2:178599380;178599379;178599378 | chr2:179464107;179464106;179464105 |
| N2AB | 17164 | 51715;51716;51717 | chr2:178599380;178599379;178599378 | chr2:179464107;179464106;179464105 |
| N2A | 16237 | 48934;48935;48936 | chr2:178599380;178599379;178599378 | chr2:179464107;179464106;179464105 |
| N2B | 9740 | 29443;29444;29445 | chr2:178599380;178599379;178599378 | chr2:179464107;179464106;179464105 |
| Novex-1 | 9865 | 29818;29819;29820 | chr2:178599380;178599379;178599378 | chr2:179464107;179464106;179464105 |
| Novex-2 | 9932 | 30019;30020;30021 | chr2:178599380;178599379;178599378 | chr2:179464107;179464106;179464105 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs759563590  |
-0.419 | 0.999 | N | 0.721 | 0.481 | 0.520320716586 | gnomAD-2.1.1 | 4.36E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.46E-06 | 0 |
| S/C | rs759563590 |
-0.419 | 0.999 | N | 0.721 | 0.481 | 0.520320716586 | gnomAD-4.0.0 | 1.63838E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.91182E-06 | 0 | 0 |
| S/F | rs759563590 |
None | 0.984 | D | 0.757 | 0.523 | 0.656847193988 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/F | rs759563590 |
None | 0.984 | D | 0.757 | 0.523 | 0.656847193988 | gnomAD-4.0.0 | 6.57575E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47076E-05 | 0 | 0 |
| S/P | rs767581453 |
-0.28 | 0.984 | D | 0.713 | 0.444 | 0.431602765429 | gnomAD-2.1.1 | 1.75E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.88E-05 | 1.89E-05 | 1.81884E-04 |
| S/P | rs767581453 |
-0.28 | 0.984 | D | 0.713 | 0.444 | 0.431602765429 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 0 | 0 | 0 |
| S/P | rs767581453 |
-0.28 | 0.984 | D | 0.713 | 0.444 | 0.431602765429 | gnomAD-4.0.0 | 1.44338E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 4.75798E-05 | 0 | 4.86315E-06 | 0 | 1.74459E-04 |
| S/Y | None | None | 0.995 | N | 0.768 | 0.493 | 0.642324679019 | gnomAD-4.0.0 | 1.63838E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.09272E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0929 | likely_benign | 0.0948 | benign | -0.604 | Destabilizing | 0.046 | N | 0.265 | neutral | N | 0.492049923 | None | None | N |
| S/C | 0.1077 | likely_benign | 0.11 | benign | -0.376 | Destabilizing | 0.999 | D | 0.721 | prob.delet. | N | 0.487304809 | None | None | N |
| S/D | 0.6702 | likely_pathogenic | 0.6733 | pathogenic | -0.825 | Destabilizing | 0.919 | D | 0.635 | neutral | None | None | None | None | N |
| S/E | 0.6339 | likely_pathogenic | 0.6181 | pathogenic | -0.677 | Destabilizing | 0.919 | D | 0.651 | neutral | None | None | None | None | N |
| S/F | 0.2251 | likely_benign | 0.2476 | benign | -0.427 | Destabilizing | 0.984 | D | 0.757 | deleterious | D | 0.524905671 | None | None | N |
| S/G | 0.1426 | likely_benign | 0.1473 | benign | -0.984 | Destabilizing | 0.825 | D | 0.61 | neutral | None | None | None | None | N |
| S/H | 0.3387 | likely_benign | 0.3323 | benign | -1.389 | Destabilizing | 0.999 | D | 0.721 | prob.delet. | None | None | None | None | N |
| S/I | 0.2073 | likely_benign | 0.219 | benign | 0.339 | Stabilizing | 0.976 | D | 0.722 | prob.delet. | None | None | None | None | N |
| S/K | 0.6433 | likely_pathogenic | 0.6244 | pathogenic | -0.28 | Destabilizing | 0.919 | D | 0.654 | neutral | None | None | None | None | N |
| S/L | 0.1085 | likely_benign | 0.1138 | benign | 0.339 | Stabilizing | 0.851 | D | 0.715 | prob.delet. | None | None | None | None | N |
| S/M | 0.2031 | likely_benign | 0.2121 | benign | 0.244 | Stabilizing | 0.999 | D | 0.723 | prob.delet. | None | None | None | None | N |
| S/N | 0.248 | likely_benign | 0.2617 | benign | -0.738 | Destabilizing | 0.919 | D | 0.623 | neutral | None | None | None | None | N |
| S/P | 0.9603 | likely_pathogenic | 0.9639 | pathogenic | 0.061 | Stabilizing | 0.984 | D | 0.713 | prob.delet. | D | 0.524905671 | None | None | N |
| S/Q | 0.4715 | ambiguous | 0.4596 | ambiguous | -0.565 | Destabilizing | 0.988 | D | 0.693 | prob.neutral | None | None | None | None | N |
| S/R | 0.5354 | ambiguous | 0.5182 | ambiguous | -0.579 | Destabilizing | 0.988 | D | 0.725 | prob.delet. | None | None | None | None | N |
| S/T | 0.0832 | likely_benign | 0.0854 | benign | -0.494 | Destabilizing | 0.103 | N | 0.447 | neutral | N | 0.495068798 | None | None | N |
| S/V | 0.211 | likely_benign | 0.2159 | benign | 0.061 | Stabilizing | 0.851 | D | 0.721 | prob.delet. | None | None | None | None | N |
| S/W | 0.3569 | ambiguous | 0.3605 | ambiguous | -0.647 | Destabilizing | 0.999 | D | 0.794 | deleterious | None | None | None | None | N |
| S/Y | 0.2143 | likely_benign | 0.2226 | benign | -0.22 | Destabilizing | 0.995 | D | 0.768 | deleterious | N | 0.506801416 | 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.