Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23394 | 70405;70406;70407 | chr2:178575952;178575951;178575950 | chr2:179440679;179440678;179440677 |
| N2AB | 21753 | 65482;65483;65484 | chr2:178575952;178575951;178575950 | chr2:179440679;179440678;179440677 |
| N2A | 20826 | 62701;62702;62703 | chr2:178575952;178575951;178575950 | chr2:179440679;179440678;179440677 |
| N2B | 14329 | 43210;43211;43212 | chr2:178575952;178575951;178575950 | chr2:179440679;179440678;179440677 |
| Novex-1 | 14454 | 43585;43586;43587 | chr2:178575952;178575951;178575950 | chr2:179440679;179440678;179440677 |
| Novex-2 | 14521 | 43786;43787;43788 | chr2:178575952;178575951;178575950 | chr2:179440679;179440678;179440677 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | None | None | 0.999 | N | 0.469 | 0.549 | 0.441740949975 | gnomAD-4.0.0 | 1.59623E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87167E-06 | 0 | 0 |
| T/M | rs397517683  |
-0.016 | 1.0 | N | 0.651 | 0.499 | 0.661236301376 | gnomAD-2.1.1 | 2.41E-05 | None | None | None | None | N | None | 0 | 8.7E-05 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 1.78E-05 | 0 |
| T/M | rs397517683 |
-0.016 | 1.0 | N | 0.651 | 0.499 | 0.661236301376 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93949E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/M | rs397517683 |
-0.016 | 1.0 | N | 0.651 | 0.499 | 0.661236301376 | gnomAD-4.0.0 | 3.16485E-05 | None | None | None | None | N | None | 0 | 5.00517E-05 | None | 0 | 6.69822E-05 | None | 0 | 0 | 3.73517E-05 | 1.09873E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.4236 | ambiguous | 0.4646 | ambiguous | -0.608 | Destabilizing | 0.999 | D | 0.469 | neutral | N | 0.483263701 | None | None | N |
| T/C | 0.867 | likely_pathogenic | 0.9009 | pathogenic | -0.297 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| T/D | 0.7962 | likely_pathogenic | 0.8304 | pathogenic | 0.644 | Stabilizing | 1.0 | D | 0.672 | neutral | None | None | None | None | N |
| T/E | 0.8392 | likely_pathogenic | 0.8652 | pathogenic | 0.594 | Stabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | N |
| T/F | 0.9031 | likely_pathogenic | 0.9287 | pathogenic | -1.002 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| T/G | 0.5483 | ambiguous | 0.6016 | pathogenic | -0.767 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| T/H | 0.7193 | likely_pathogenic | 0.7799 | pathogenic | -0.981 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| T/I | 0.8577 | likely_pathogenic | 0.9019 | pathogenic | -0.298 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| T/K | 0.6787 | likely_pathogenic | 0.7273 | pathogenic | -0.255 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | N | 0.511585407 | None | None | N |
| T/L | 0.5225 | ambiguous | 0.5813 | pathogenic | -0.298 | Destabilizing | 0.999 | D | 0.589 | neutral | None | None | None | None | N |
| T/M | 0.3549 | ambiguous | 0.4118 | ambiguous | -0.117 | Destabilizing | 1.0 | D | 0.651 | neutral | N | 0.516625055 | None | None | N |
| T/N | 0.3833 | ambiguous | 0.4293 | ambiguous | -0.093 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| T/P | 0.7713 | likely_pathogenic | 0.8238 | pathogenic | -0.372 | Destabilizing | 1.0 | D | 0.65 | neutral | N | 0.487164495 | None | None | N |
| T/Q | 0.6845 | likely_pathogenic | 0.7226 | pathogenic | -0.264 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| T/R | 0.6281 | likely_pathogenic | 0.6861 | pathogenic | -0.047 | Destabilizing | 1.0 | D | 0.663 | neutral | D | 0.529941881 | None | None | N |
| T/S | 0.2646 | likely_benign | 0.2953 | benign | -0.428 | Destabilizing | 0.999 | D | 0.469 | neutral | N | 0.471875012 | None | None | N |
| T/V | 0.7061 | likely_pathogenic | 0.7761 | pathogenic | -0.372 | Destabilizing | 0.999 | D | 0.514 | neutral | None | None | None | None | N |
| T/W | 0.9613 | likely_pathogenic | 0.9746 | pathogenic | -0.949 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| T/Y | 0.8808 | likely_pathogenic | 0.9171 | pathogenic | -0.683 | Destabilizing | 1.0 | D | 0.735 | 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.