Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21590 | 64993;64994;64995 | chr2:178584873;178584872;178584871 | chr2:179449600;179449599;179449598 |
| N2AB | 19949 | 60070;60071;60072 | chr2:178584873;178584872;178584871 | chr2:179449600;179449599;179449598 |
| N2A | 19022 | 57289;57290;57291 | chr2:178584873;178584872;178584871 | chr2:179449600;179449599;179449598 |
| N2B | 12525 | 37798;37799;37800 | chr2:178584873;178584872;178584871 | chr2:179449600;179449599;179449598 |
| Novex-1 | 12650 | 38173;38174;38175 | chr2:178584873;178584872;178584871 | chr2:179449600;179449599;179449598 |
| Novex-2 | 12717 | 38374;38375;38376 | chr2:178584873;178584872;178584871 | chr2:179449600;179449599;179449598 |
| 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/G | rs768922798  |
-1.477 | 0.892 | N | 0.585 | 0.232 | 0.226586394389 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| S/G | rs768922798 |
-1.477 | 0.892 | N | 0.585 | 0.232 | 0.226586394389 | gnomAD-4.0.0 | 1.59209E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43303E-05 | 0 |
| S/N | rs972890341 |
-0.904 | 0.892 | N | 0.699 | 0.329 | 0.28297238246 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| S/N | rs972890341 |
-0.904 | 0.892 | N | 0.699 | 0.329 | 0.28297238246 | gnomAD-4.0.0 | 4.10619E-06 | None | None | None | None | I | None | 0 | 2.23704E-05 | None | 0 | 0 | None | 0 | 1.73611E-04 | 3.59847E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.2085 | likely_benign | 0.184 | benign | -0.932 | Destabilizing | 0.818 | D | 0.613 | neutral | None | None | None | None | I |
| S/C | 0.1684 | likely_benign | 0.1459 | benign | -0.551 | Destabilizing | 0.999 | D | 0.668 | neutral | N | 0.495972875 | None | None | I |
| S/D | 0.9703 | likely_pathogenic | 0.9672 | pathogenic | -0.351 | Destabilizing | 0.957 | D | 0.712 | prob.delet. | None | None | None | None | I |
| S/E | 0.9745 | likely_pathogenic | 0.9738 | pathogenic | -0.367 | Destabilizing | 0.916 | D | 0.654 | neutral | None | None | None | None | I |
| S/F | 0.8813 | likely_pathogenic | 0.8532 | pathogenic | -1.216 | Destabilizing | 0.996 | D | 0.717 | prob.delet. | None | None | None | None | I |
| S/G | 0.278 | likely_benign | 0.2495 | benign | -1.158 | Destabilizing | 0.892 | D | 0.585 | neutral | N | 0.462095485 | None | None | I |
| S/H | 0.9237 | likely_pathogenic | 0.9222 | pathogenic | -1.637 | Destabilizing | 0.997 | D | 0.665 | neutral | None | None | None | None | I |
| S/I | 0.806 | likely_pathogenic | 0.7881 | pathogenic | -0.434 | Destabilizing | 0.983 | D | 0.711 | prob.delet. | N | 0.516695555 | None | None | I |
| S/K | 0.9936 | likely_pathogenic | 0.9936 | pathogenic | -0.76 | Destabilizing | 0.845 | D | 0.625 | neutral | None | None | None | None | I |
| S/L | 0.6199 | likely_pathogenic | 0.5907 | pathogenic | -0.434 | Destabilizing | 0.916 | D | 0.696 | prob.neutral | None | None | None | None | I |
| S/M | 0.6589 | likely_pathogenic | 0.6277 | pathogenic | None | Stabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | I |
| S/N | 0.7092 | likely_pathogenic | 0.6696 | pathogenic | -0.683 | Destabilizing | 0.892 | D | 0.699 | prob.neutral | N | 0.500072557 | None | None | I |
| S/P | 0.9944 | likely_pathogenic | 0.9945 | pathogenic | -0.568 | Destabilizing | 0.996 | D | 0.685 | prob.neutral | None | None | None | None | I |
| S/Q | 0.9419 | likely_pathogenic | 0.943 | pathogenic | -0.887 | Destabilizing | 0.975 | D | 0.717 | prob.delet. | None | None | None | None | I |
| S/R | 0.9862 | likely_pathogenic | 0.9867 | pathogenic | -0.604 | Destabilizing | 0.056 | N | 0.534 | neutral | N | 0.47730704 | None | None | I |
| S/T | 0.3143 | likely_benign | 0.2586 | benign | -0.733 | Destabilizing | 0.892 | D | 0.637 | neutral | N | 0.478587714 | None | None | I |
| S/V | 0.7023 | likely_pathogenic | 0.6653 | pathogenic | -0.568 | Destabilizing | 0.987 | D | 0.702 | prob.neutral | None | None | None | None | I |
| S/W | 0.9277 | likely_pathogenic | 0.9302 | pathogenic | -1.145 | Destabilizing | 0.999 | D | 0.76 | deleterious | None | None | None | None | I |
| S/Y | 0.8527 | likely_pathogenic | 0.8341 | pathogenic | -0.905 | Destabilizing | 0.996 | D | 0.718 | prob.delet. | 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.