Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30462 | 91609;91610;91611 | chr2:178551147;178551146;178551145 | chr2:179415874;179415873;179415872 |
| N2AB | 28821 | 86686;86687;86688 | chr2:178551147;178551146;178551145 | chr2:179415874;179415873;179415872 |
| N2A | 27894 | 83905;83906;83907 | chr2:178551147;178551146;178551145 | chr2:179415874;179415873;179415872 |
| N2B | 21397 | 64414;64415;64416 | chr2:178551147;178551146;178551145 | chr2:179415874;179415873;179415872 |
| Novex-1 | 21522 | 64789;64790;64791 | chr2:178551147;178551146;178551145 | chr2:179415874;179415873;179415872 |
| Novex-2 | 21589 | 64990;64991;64992 | chr2:178551147;178551146;178551145 | chr2:179415874;179415873;179415872 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs794729529  |
-1.001 | 1.0 | N | 0.69 | 0.444 | 0.28058544554 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 2.67E-05 | 0 |
| R/Q | rs794729529 |
-1.001 | 1.0 | N | 0.69 | 0.444 | 0.28058544554 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 2.07125E-04 | 0 |
| R/Q | rs794729529 |
-1.001 | 1.0 | N | 0.69 | 0.444 | 0.28058544554 | gnomAD-4.0.0 | 2.85122E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.23204E-05 | None | 1.56294E-05 | 0 | 3.39085E-05 | 2.19597E-05 | 3.20287E-05 |
| R/W | rs373623340 |
-0.833 | 1.0 | N | 0.88 | 0.474 | None | gnomAD-2.1.1 | 5.36E-05 | None | None | None | None | N | None | 4.54959E-04 | 2.83E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.57E-05 | 0 |
| R/W | rs373623340 |
-0.833 | 1.0 | N | 0.88 | 0.474 | None | gnomAD-3.1.2 | 1.0523E-04 | None | None | None | None | N | None | 3.62301E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/W | rs373623340 |
-0.833 | 1.0 | N | 0.88 | 0.474 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 2.3E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/W | rs373623340 |
-0.833 | 1.0 | N | 0.88 | 0.474 | None | gnomAD-4.0.0 | 2.29324E-05 | None | None | None | None | N | None | 3.33431E-04 | 1.66733E-05 | None | 0 | 0 | None | 0 | 3.30142E-04 | 1.69542E-06 | 1.09815E-05 | 9.60523E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.934 | likely_pathogenic | 0.9487 | pathogenic | -1.663 | Destabilizing | 0.999 | D | 0.583 | neutral | None | None | None | None | N |
| R/C | 0.4535 | ambiguous | 0.497 | ambiguous | -1.646 | Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | None | N |
| R/D | 0.9877 | likely_pathogenic | 0.99 | pathogenic | -0.706 | Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| R/E | 0.9094 | likely_pathogenic | 0.9242 | pathogenic | -0.52 | Destabilizing | 0.999 | D | 0.573 | neutral | None | None | None | None | N |
| R/F | 0.9053 | likely_pathogenic | 0.9299 | pathogenic | -1.082 | Destabilizing | 1.0 | D | 0.892 | deleterious | None | None | None | None | N |
| R/G | 0.8477 | likely_pathogenic | 0.8836 | pathogenic | -2.008 | Highly Destabilizing | 1.0 | D | 0.798 | deleterious | N | 0.496464933 | None | None | N |
| R/H | 0.3016 | likely_benign | 0.3255 | benign | -1.972 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| R/I | 0.8471 | likely_pathogenic | 0.872 | pathogenic | -0.686 | Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| R/K | 0.1698 | likely_benign | 0.1751 | benign | -1.364 | Destabilizing | 0.998 | D | 0.449 | neutral | None | None | None | None | N |
| R/L | 0.6954 | likely_pathogenic | 0.7303 | pathogenic | -0.686 | Destabilizing | 1.0 | D | 0.798 | deleterious | N | 0.484183575 | None | None | N |
| R/M | 0.7576 | likely_pathogenic | 0.8021 | pathogenic | -1.108 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| R/N | 0.9537 | likely_pathogenic | 0.9639 | pathogenic | -1.093 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| R/P | 0.9945 | likely_pathogenic | 0.9958 | pathogenic | -0.997 | Destabilizing | 1.0 | D | 0.892 | deleterious | D | 0.523216469 | None | None | N |
| R/Q | 0.2774 | likely_benign | 0.2977 | benign | -1.084 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | N | 0.466266676 | None | None | N |
| R/S | 0.9601 | likely_pathogenic | 0.9702 | pathogenic | -1.985 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| R/T | 0.9249 | likely_pathogenic | 0.9454 | pathogenic | -1.596 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| R/V | 0.8897 | likely_pathogenic | 0.9093 | pathogenic | -0.997 | Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| R/W | 0.6015 | likely_pathogenic | 0.6585 | pathogenic | -0.608 | Destabilizing | 1.0 | D | 0.88 | deleterious | N | 0.480967571 | None | None | N |
| R/Y | 0.7836 | likely_pathogenic | 0.8209 | pathogenic | -0.405 | Destabilizing | 1.0 | D | 0.911 | 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.