Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31631 | 95116;95117;95118 | chr2:178546440;178546439;178546438 | chr2:179411167;179411166;179411165 |
| N2AB | 29990 | 90193;90194;90195 | chr2:178546440;178546439;178546438 | chr2:179411167;179411166;179411165 |
| N2A | 29063 | 87412;87413;87414 | chr2:178546440;178546439;178546438 | chr2:179411167;179411166;179411165 |
| N2B | 22566 | 67921;67922;67923 | chr2:178546440;178546439;178546438 | chr2:179411167;179411166;179411165 |
| Novex-1 | 22691 | 68296;68297;68298 | chr2:178546440;178546439;178546438 | chr2:179411167;179411166;179411165 |
| Novex-2 | 22758 | 68497;68498;68499 | chr2:178546440;178546439;178546438 | chr2:179411167;179411166;179411165 |
| 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/F | rs765646839  |
-1.272 | 1.0 | N | 0.741 | 0.455 | 0.609617904835 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 0 | 0 |
| S/F | rs765646839 |
-1.272 | 1.0 | N | 0.741 | 0.455 | 0.609617904835 | gnomAD-4.0.0 | 3.18303E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77562E-05 | None | 0 | 0 | 0 | 1.43295E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1103 | likely_benign | 0.1124 | benign | -0.572 | Destabilizing | 0.997 | D | 0.455 | neutral | N | 0.500615399 | None | None | N |
| S/C | 0.1491 | likely_benign | 0.1509 | benign | -0.348 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | N | 0.503271702 | None | None | N |
| S/D | 0.6363 | likely_pathogenic | 0.644 | pathogenic | -0.137 | Destabilizing | 0.999 | D | 0.644 | neutral | None | None | None | None | N |
| S/E | 0.7037 | likely_pathogenic | 0.7017 | pathogenic | -0.202 | Destabilizing | 0.999 | D | 0.617 | neutral | None | None | None | None | N |
| S/F | 0.3967 | ambiguous | 0.4141 | ambiguous | -0.982 | Destabilizing | 1.0 | D | 0.741 | deleterious | N | 0.490232011 | None | None | N |
| S/G | 0.1478 | likely_benign | 0.1476 | benign | -0.744 | Destabilizing | 0.999 | D | 0.473 | neutral | None | None | None | None | N |
| S/H | 0.5527 | ambiguous | 0.5452 | ambiguous | -1.285 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| S/I | 0.4511 | ambiguous | 0.4667 | ambiguous | -0.237 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| S/K | 0.8854 | likely_pathogenic | 0.8808 | pathogenic | -0.678 | Destabilizing | 0.999 | D | 0.632 | neutral | None | None | None | None | N |
| S/L | 0.179 | likely_benign | 0.1938 | benign | -0.237 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | N |
| S/M | 0.2608 | likely_benign | 0.2755 | benign | 0.137 | Stabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| S/N | 0.2322 | likely_benign | 0.2374 | benign | -0.458 | Destabilizing | 0.999 | D | 0.613 | neutral | None | None | None | None | N |
| S/P | 0.9826 | likely_pathogenic | 0.9787 | pathogenic | -0.318 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | N | 0.489725031 | None | None | N |
| S/Q | 0.6467 | likely_pathogenic | 0.637 | pathogenic | -0.719 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| S/R | 0.8497 | likely_pathogenic | 0.8393 | pathogenic | -0.461 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | N |
| S/T | 0.1117 | likely_benign | 0.1178 | benign | -0.534 | Destabilizing | 0.999 | D | 0.463 | neutral | N | 0.502058194 | None | None | N |
| S/V | 0.3496 | ambiguous | 0.3682 | ambiguous | -0.318 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| S/W | 0.5848 | likely_pathogenic | 0.5834 | pathogenic | -0.947 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| S/Y | 0.358 | ambiguous | 0.3688 | ambiguous | -0.698 | Destabilizing | 1.0 | D | 0.746 | deleterious | N | 0.463480475 | 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.