Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8320 | 25183;25184;25185 | chr2:178718048;178718047;178718046 | chr2:179582775;179582774;179582773 |
| N2AB | 8003 | 24232;24233;24234 | chr2:178718048;178718047;178718046 | chr2:179582775;179582774;179582773 |
| N2A | 7076 | 21451;21452;21453 | chr2:178718048;178718047;178718046 | chr2:179582775;179582774;179582773 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/C | rs1374151646  |
None | 0.955 | D | 0.689 | 0.368 | 0.541285430251 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 1.47E-05 | 0 | 0 |
| S/C | rs1374151646 |
None | 0.955 | D | 0.689 | 0.368 | 0.541285430251 | gnomAD-4.0.0 | 1.31377E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.40136E-03 | 1.47059E-05 | 0 | 0 |
| S/F | rs1374151646 |
-0.508 | 0.988 | N | 0.753 | 0.4 | 0.732106347842 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65782E-04 |
| S/F | rs1374151646 |
-0.508 | 0.988 | N | 0.753 | 0.4 | 0.732106347842 | gnomAD-4.0.0 | 4.77415E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.41196E-04 | 2.85868E-06 | 0 | 3.02371E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0909 | likely_benign | 0.098 | benign | -0.68 | Destabilizing | None | N | 0.209 | neutral | D | 0.530443313 | None | None | N |
| S/C | 0.1115 | likely_benign | 0.1228 | benign | -0.522 | Destabilizing | 0.955 | D | 0.689 | prob.neutral | D | 0.53435041 | None | None | N |
| S/D | 0.5934 | likely_pathogenic | 0.6869 | pathogenic | -1.33 | Destabilizing | 0.798 | D | 0.557 | neutral | None | None | None | None | N |
| S/E | 0.5413 | ambiguous | 0.5968 | pathogenic | -1.162 | Destabilizing | 0.694 | D | 0.526 | neutral | None | None | None | None | N |
| S/F | 0.1479 | likely_benign | 0.1707 | benign | -0.448 | Destabilizing | 0.988 | D | 0.753 | deleterious | N | 0.498382669 | None | None | N |
| S/G | 0.1589 | likely_benign | 0.2044 | benign | -1.064 | Destabilizing | 0.01 | N | 0.211 | neutral | None | None | None | None | N |
| S/H | 0.2968 | likely_benign | 0.3424 | ambiguous | -1.492 | Destabilizing | 0.997 | D | 0.688 | prob.neutral | None | None | None | None | N |
| S/I | 0.1309 | likely_benign | 0.1519 | benign | 0.286 | Stabilizing | 0.753 | D | 0.674 | neutral | None | None | None | None | N |
| S/K | 0.6401 | likely_pathogenic | 0.6974 | pathogenic | -0.419 | Destabilizing | 0.753 | D | 0.533 | neutral | None | None | None | None | N |
| S/L | 0.0941 | likely_benign | 0.1104 | benign | 0.286 | Stabilizing | 0.753 | D | 0.667 | neutral | None | None | None | None | N |
| S/M | 0.1675 | likely_benign | 0.183 | benign | 0.165 | Stabilizing | 0.991 | D | 0.695 | prob.neutral | None | None | None | None | N |
| S/N | 0.1747 | likely_benign | 0.2199 | benign | -0.98 | Destabilizing | 0.316 | N | 0.531 | neutral | None | None | None | None | N |
| S/P | 0.9636 | likely_pathogenic | 0.9808 | pathogenic | None | Stabilizing | 0.858 | D | 0.691 | prob.neutral | N | 0.519462665 | None | None | N |
| S/Q | 0.4546 | ambiguous | 0.5195 | ambiguous | -0.761 | Destabilizing | 0.936 | D | 0.632 | neutral | None | None | None | None | N |
| S/R | 0.5179 | ambiguous | 0.5879 | pathogenic | -0.756 | Destabilizing | 0.044 | N | 0.51 | neutral | None | None | None | None | N |
| S/T | 0.0675 | likely_benign | 0.0688 | benign | -0.651 | Destabilizing | 0.001 | N | 0.199 | neutral | N | 0.425273144 | None | None | N |
| S/V | 0.139 | likely_benign | 0.151 | benign | None | Stabilizing | 0.03 | N | 0.521 | neutral | None | None | None | None | N |
| S/W | 0.2896 | likely_benign | 0.345 | ambiguous | -0.744 | Destabilizing | 0.999 | D | 0.742 | deleterious | None | None | None | None | N |
| S/Y | 0.1378 | likely_benign | 0.1552 | benign | -0.299 | Destabilizing | 0.996 | D | 0.748 | deleterious | N | 0.498889648 | 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.