Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 62 | 409;410;411 | chr2:178802249;178802248;178802247 | chr2:179666976;179666975;179666974 |
| N2AB | 62 | 409;410;411 | chr2:178802249;178802248;178802247 | chr2:179666976;179666975;179666974 |
| N2A | 62 | 409;410;411 | chr2:178802249;178802248;178802247 | chr2:179666976;179666975;179666974 |
| N2B | 62 | 409;410;411 | chr2:178802249;178802248;178802247 | chr2:179666976;179666975;179666974 |
| Novex-1 | 62 | 409;410;411 | chr2:178802249;178802248;178802247 | chr2:179666976;179666975;179666974 |
| Novex-2 | 62 | 409;410;411 | chr2:178802249;178802248;178802247 | chr2:179666976;179666975;179666974 |
| Novex-3 | 62 | 409;410;411 | chr2:178802249;178802248;178802247 | chr2:179666976;179666975;179666974 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs766108359  |
-0.905 | 1.0 | D | 0.741 | 0.561 | 0.789176987369 | gnomAD-2.1.1 | 1.19E-05 | None | None | None | -0.054(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.64E-05 | 0 |
| R/C | rs766108359 |
-0.905 | 1.0 | D | 0.741 | 0.561 | 0.789176987369 | gnomAD-4.0.0 | 4.10443E-06 | None | None | None | -0.054(TCAP) | N | None | 0 | 0 | None | 3.82614E-05 | 0 | None | 0 | 0 | 2.69789E-06 | 2.31863E-05 | 0 |
| R/G | None | None | 1.0 | N | 0.69 | 0.621 | 0.690662525078 | gnomAD-4.0.0 | 6.84071E-07 | None | None | None | -0.371(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99295E-07 | 0 | 0 |
| R/H | rs758169489 |
-1.574 | 1.0 | N | 0.748 | 0.499 | None | gnomAD-2.1.1 | 7.78E-05 | None | None | None | 0.037(TCAP) | N | None | 4.01E-05 | 0 | None | 0 | 8.53328E-04 | None | 9.8E-05 | None | 0 | 7.75E-06 | 0 |
| R/H | rs758169489 |
-1.574 | 1.0 | N | 0.748 | 0.499 | None | gnomAD-3.1.2 | 3.95E-05 | None | None | None | 0.037(TCAP) | N | None | 4.83E-05 | 0 | 0 | 0 | 3.86698E-04 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/H | rs758169489 |
-1.574 | 1.0 | N | 0.748 | 0.499 | None | gnomAD-4.0.0 | 1.85888E-05 | None | None | None | 0.037(TCAP) | N | None | 2.67173E-05 | 0 | None | 0 | 3.1211E-04 | None | 0 | 0 | 8.47455E-06 | 3.29366E-05 | 1.60036E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.3979 | ambiguous | 0.4306 | ambiguous | -0.74 | Destabilizing | 0.999 | D | 0.657 | neutral | None | None | None | -0.449(TCAP) | N |
| R/C | 0.2379 | likely_benign | 0.2641 | benign | -0.546 | Destabilizing | 1.0 | D | 0.741 | deleterious | D | 0.537617579 | None | -0.054(TCAP) | N |
| R/D | 0.7369 | likely_pathogenic | 0.7552 | pathogenic | -0.142 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | 0.29(TCAP) | N |
| R/E | 0.3467 | ambiguous | 0.3607 | ambiguous | -0.02 | Destabilizing | 0.997 | D | 0.684 | prob.neutral | None | None | None | 0.219(TCAP) | N |
| R/F | 0.4538 | ambiguous | 0.4843 | ambiguous | -0.577 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | -0.468(TCAP) | N |
| R/G | 0.3654 | ambiguous | 0.3801 | ambiguous | -1.061 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | N | 0.474042299 | None | -0.371(TCAP) | N |
| R/H | 0.0838 | likely_benign | 0.0896 | benign | -1.453 | Destabilizing | 1.0 | D | 0.748 | deleterious | N | 0.495235923 | None | 0.037(TCAP) | N |
| R/I | 0.1758 | likely_benign | 0.1832 | benign | 0.127 | Stabilizing | 0.999 | D | 0.756 | deleterious | None | None | None | -0.7(TCAP) | N |
| R/K | 0.0996 | likely_benign | 0.1001 | benign | -0.796 | Destabilizing | 0.979 | D | 0.526 | neutral | None | None | None | 0.166(TCAP) | N |
| R/L | 0.1856 | likely_benign | 0.2052 | benign | 0.127 | Stabilizing | 1.0 | D | 0.69 | prob.neutral | N | 0.43477 | None | -0.7(TCAP) | N |
| R/M | 0.2416 | likely_benign | 0.2416 | benign | -0.115 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | -0.27(TCAP) | N |
| R/N | 0.5572 | ambiguous | 0.5764 | pathogenic | -0.205 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | 0.065(TCAP) | N |
| R/P | 0.9337 | likely_pathogenic | 0.9344 | pathogenic | -0.141 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | N | 0.51391892 | None | -0.615(TCAP) | N |
| R/Q | 0.0894 | likely_benign | 0.093 | benign | -0.369 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | 0.06(TCAP) | N |
| R/S | 0.4533 | ambiguous | 0.4854 | ambiguous | -0.917 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | N | 0.405205919 | None | 0.34(TCAP) | N |
| R/T | 0.2036 | likely_benign | 0.2118 | benign | -0.614 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | 0.275(TCAP) | N |
| R/V | 0.2537 | likely_benign | 0.2764 | benign | -0.141 | Destabilizing | 0.999 | D | 0.749 | deleterious | None | None | None | -0.615(TCAP) | N |
| R/W | 0.1752 | likely_benign | 0.1875 | benign | -0.254 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | -0.279(TCAP) | N |
| R/Y | 0.3603 | ambiguous | 0.3808 | ambiguous | 0.045 | Stabilizing | 0.999 | D | 0.757 | deleterious | None | None | None | -0.274(TCAP) | 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.