Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31389 | 94390;94391;94392 | chr2:178547461;178547460;178547459 | chr2:179412188;179412187;179412186 |
| N2AB | 29748 | 89467;89468;89469 | chr2:178547461;178547460;178547459 | chr2:179412188;179412187;179412186 |
| N2A | 28821 | 86686;86687;86688 | chr2:178547461;178547460;178547459 | chr2:179412188;179412187;179412186 |
| N2B | 22324 | 67195;67196;67197 | chr2:178547461;178547460;178547459 | chr2:179412188;179412187;179412186 |
| Novex-1 | 22449 | 67570;67571;67572 | chr2:178547461;178547460;178547459 | chr2:179412188;179412187;179412186 |
| Novex-2 | 22516 | 67771;67772;67773 | chr2:178547461;178547460;178547459 | chr2:179412188;179412187;179412186 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/C | None | None | 0.995 | N | 0.714 | 0.396 | 0.562428738172 | gnomAD-4.0.0 | 6.85099E-07 | None | None | None | None | I | None | 2.98972E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| F/L | rs1232852062  |
-0.215 | 0.722 | N | 0.498 | 0.302 | 0.188950314367 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.3E-05 | None | 0 | 0 | 0 |
| F/L | rs1232852062 |
-0.215 | 0.722 | N | 0.498 | 0.302 | 0.188950314367 | gnomAD-4.0.0 | 2.74035E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.64695E-05 | 0 |
| F/Y | rs747608895 |
-0.008 | 0.034 | N | 0.385 | 0.17 | 0.212008924253 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | I | None | 0 | 2.94E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| F/Y | rs747608895 |
-0.008 | 0.034 | N | 0.385 | 0.17 | 0.212008924253 | gnomAD-4.0.0 | 6.85099E-07 | None | None | None | None | I | None | 0 | 2.24931E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.972 | likely_pathogenic | 0.957 | pathogenic | -0.929 | Destabilizing | 0.633 | D | 0.609 | neutral | None | None | None | None | I |
| F/C | 0.9045 | likely_pathogenic | 0.8223 | pathogenic | -0.238 | Destabilizing | 0.995 | D | 0.714 | prob.delet. | N | 0.478403048 | None | None | I |
| F/D | 0.9877 | likely_pathogenic | 0.9847 | pathogenic | 0.643 | Stabilizing | 0.923 | D | 0.683 | prob.neutral | None | None | None | None | I |
| F/E | 0.9917 | likely_pathogenic | 0.9895 | pathogenic | 0.616 | Stabilizing | 0.923 | D | 0.653 | neutral | None | None | None | None | I |
| F/G | 0.9867 | likely_pathogenic | 0.9814 | pathogenic | -1.12 | Destabilizing | 0.633 | D | 0.633 | neutral | None | None | None | None | I |
| F/H | 0.9103 | likely_pathogenic | 0.8823 | pathogenic | 0.261 | Stabilizing | 0.961 | D | 0.602 | neutral | None | None | None | None | I |
| F/I | 0.8677 | likely_pathogenic | 0.8074 | pathogenic | -0.447 | Destabilizing | 0.949 | D | 0.513 | neutral | N | 0.42547264 | None | None | I |
| F/K | 0.9929 | likely_pathogenic | 0.9908 | pathogenic | -0.037 | Destabilizing | 0.858 | D | 0.659 | neutral | None | None | None | None | I |
| F/L | 0.9915 | likely_pathogenic | 0.9876 | pathogenic | -0.447 | Destabilizing | 0.722 | D | 0.498 | neutral | N | 0.481115279 | None | None | I |
| F/M | 0.9334 | likely_pathogenic | 0.8973 | pathogenic | -0.357 | Destabilizing | 0.987 | D | 0.528 | neutral | None | None | None | None | I |
| F/N | 0.9577 | likely_pathogenic | 0.946 | pathogenic | 0.021 | Stabilizing | 0.858 | D | 0.693 | prob.neutral | None | None | None | None | I |
| F/P | 0.9993 | likely_pathogenic | 0.9992 | pathogenic | -0.589 | Destabilizing | 0.961 | D | 0.702 | prob.neutral | None | None | None | None | I |
| F/Q | 0.9822 | likely_pathogenic | 0.9756 | pathogenic | -0.054 | Destabilizing | 0.923 | D | 0.7 | prob.neutral | None | None | None | None | I |
| F/R | 0.9808 | likely_pathogenic | 0.9755 | pathogenic | 0.437 | Stabilizing | 0.923 | D | 0.697 | prob.neutral | None | None | None | None | I |
| F/S | 0.9434 | likely_pathogenic | 0.9197 | pathogenic | -0.631 | Destabilizing | 0.075 | N | 0.49 | neutral | N | 0.504029424 | None | None | I |
| F/T | 0.9711 | likely_pathogenic | 0.9562 | pathogenic | -0.565 | Destabilizing | 0.633 | D | 0.618 | neutral | None | None | None | None | I |
| F/V | 0.8768 | likely_pathogenic | 0.8174 | pathogenic | -0.589 | Destabilizing | 0.722 | D | 0.613 | neutral | N | 0.451637734 | None | None | I |
| F/W | 0.7127 | likely_pathogenic | 0.6792 | pathogenic | -0.322 | Destabilizing | 0.996 | D | 0.533 | neutral | None | None | None | None | I |
| F/Y | 0.2506 | likely_benign | 0.2283 | benign | -0.288 | Destabilizing | 0.034 | N | 0.385 | neutral | N | 0.426608791 | 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.