Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14853 | 44782;44783;44784 | chr2:178624723;178624722;178624721 | chr2:179489450;179489449;179489448 |
| N2AB | 13212 | 39859;39860;39861 | chr2:178624723;178624722;178624721 | chr2:179489450;179489449;179489448 |
| N2A | 12285 | 37078;37079;37080 | chr2:178624723;178624722;178624721 | chr2:179489450;179489449;179489448 |
| N2B | 5788 | 17587;17588;17589 | chr2:178624723;178624722;178624721 | chr2:179489450;179489449;179489448 |
| Novex-1 | 5913 | 17962;17963;17964 | chr2:178624723;178624722;178624721 | chr2:179489450;179489449;179489448 |
| Novex-2 | 5980 | 18163;18164;18165 | chr2:178624723;178624722;178624721 | chr2:179489450;179489449;179489448 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1478720233  |
-1.669 | 0.543 | N | 0.37 | 0.218 | 0.359763055319 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.61E-05 | None | 0 | None | 0 | 0 | 0 |
| V/F | rs753457792 |
None | 0.999 | N | 0.715 | 0.355 | 0.62907203384 | 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 |
| V/F | rs753457792 |
None | 0.999 | N | 0.715 | 0.355 | 0.62907203384 | gnomAD-4.0.0 | 6.58172E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47245E-05 | 0 | 0 |
| V/G | None | None | 0.997 | N | 0.634 | 0.377 | 0.64568061723 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| V/I | rs753457792 |
-0.662 | 0.987 | N | 0.582 | 0.24 | 0.336155897331 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.4474 | ambiguous | 0.3411 | ambiguous | -1.235 | Destabilizing | 0.543 | D | 0.37 | neutral | N | 0.413840154 | None | None | N |
| V/C | 0.9574 | likely_pathogenic | 0.9407 | pathogenic | -0.822 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| V/D | 0.9358 | likely_pathogenic | 0.9051 | pathogenic | -0.734 | Destabilizing | 0.998 | D | 0.721 | prob.delet. | N | 0.474349863 | None | None | N |
| V/E | 0.8454 | likely_pathogenic | 0.8168 | pathogenic | -0.714 | Destabilizing | 0.999 | D | 0.677 | prob.neutral | None | None | None | None | N |
| V/F | 0.8 | likely_pathogenic | 0.7378 | pathogenic | -0.833 | Destabilizing | 0.999 | D | 0.715 | prob.delet. | N | 0.437783149 | None | None | N |
| V/G | 0.7873 | likely_pathogenic | 0.696 | pathogenic | -1.567 | Destabilizing | 0.997 | D | 0.634 | neutral | N | 0.473791932 | None | None | N |
| V/H | 0.9864 | likely_pathogenic | 0.9789 | pathogenic | -1.061 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| V/I | 0.1555 | likely_benign | 0.1357 | benign | -0.427 | Destabilizing | 0.987 | D | 0.582 | neutral | N | 0.344706066 | None | None | N |
| V/K | 0.9444 | likely_pathogenic | 0.9319 | pathogenic | -0.985 | Destabilizing | 0.999 | D | 0.678 | prob.neutral | None | None | None | None | N |
| V/L | 0.6804 | likely_pathogenic | 0.6143 | pathogenic | -0.427 | Destabilizing | 0.973 | D | 0.578 | neutral | N | 0.347057496 | None | None | N |
| V/M | 0.5901 | likely_pathogenic | 0.4906 | ambiguous | -0.414 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| V/N | 0.9153 | likely_pathogenic | 0.8842 | pathogenic | -0.787 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| V/P | 0.8471 | likely_pathogenic | 0.7896 | pathogenic | -0.66 | Destabilizing | 0.999 | D | 0.683 | prob.neutral | None | None | None | None | N |
| V/Q | 0.9042 | likely_pathogenic | 0.8881 | pathogenic | -0.889 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| V/R | 0.9164 | likely_pathogenic | 0.902 | pathogenic | -0.569 | Destabilizing | 0.999 | D | 0.741 | deleterious | None | None | None | None | N |
| V/S | 0.7113 | likely_pathogenic | 0.6225 | pathogenic | -1.357 | Destabilizing | 0.995 | D | 0.616 | neutral | None | None | None | None | N |
| V/T | 0.4458 | ambiguous | 0.3601 | ambiguous | -1.216 | Destabilizing | 0.992 | D | 0.588 | neutral | None | None | None | None | N |
| V/W | 0.9936 | likely_pathogenic | 0.9876 | pathogenic | -1.029 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| V/Y | 0.9719 | likely_pathogenic | 0.9614 | pathogenic | -0.714 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | 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.