Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27148 | 81667;81668;81669 | chr2:178564690;178564689;178564688 | chr2:179429417;179429416;179429415 |
| N2AB | 25507 | 76744;76745;76746 | chr2:178564690;178564689;178564688 | chr2:179429417;179429416;179429415 |
| N2A | 24580 | 73963;73964;73965 | chr2:178564690;178564689;178564688 | chr2:179429417;179429416;179429415 |
| N2B | 18083 | 54472;54473;54474 | chr2:178564690;178564689;178564688 | chr2:179429417;179429416;179429415 |
| Novex-1 | 18208 | 54847;54848;54849 | chr2:178564690;178564689;178564688 | chr2:179429417;179429416;179429415 |
| Novex-2 | 18275 | 55048;55049;55050 | chr2:178564690;178564689;178564688 | chr2:179429417;179429416;179429415 |
| 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/A | None | None | 0.148 | N | 0.432 | 0.202 | 0.119812018005 | gnomAD-4.0.0 | 6.8437E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99546E-07 | 0 | 0 |
| S/P | rs1705027255  |
None | 0.954 | N | 0.726 | 0.378 | 0.269558022972 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/P | rs1705027255 |
None | 0.954 | N | 0.726 | 0.378 | 0.269558022972 | gnomAD-4.0.0 | 1.23967E-06 | None | None | None | None | N | None | 2.66973E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0941 | likely_benign | 0.0842 | benign | -0.908 | Destabilizing | 0.148 | N | 0.432 | neutral | N | 0.450445656 | None | None | N |
| S/C | 0.0629 | likely_benign | 0.0622 | benign | -0.839 | Destabilizing | 0.954 | D | 0.704 | prob.neutral | N | 0.448562931 | None | None | N |
| S/D | 0.8183 | likely_pathogenic | 0.7493 | pathogenic | -2.077 | Highly Destabilizing | 0.888 | D | 0.625 | neutral | None | None | None | None | N |
| S/E | 0.7919 | likely_pathogenic | 0.7318 | pathogenic | -1.863 | Destabilizing | 0.722 | D | 0.579 | neutral | None | None | None | None | N |
| S/F | 0.1078 | likely_benign | 0.0883 | benign | -0.55 | Destabilizing | None | N | 0.461 | neutral | N | 0.44686942 | None | None | N |
| S/G | 0.1737 | likely_benign | 0.1502 | benign | -1.274 | Destabilizing | 0.517 | D | 0.571 | neutral | None | None | None | None | N |
| S/H | 0.3571 | ambiguous | 0.3259 | benign | -1.619 | Destabilizing | 0.818 | D | 0.725 | prob.delet. | None | None | None | None | N |
| S/I | 0.2031 | likely_benign | 0.1712 | benign | 0.03 | Stabilizing | 0.39 | N | 0.704 | prob.neutral | None | None | None | None | N |
| S/K | 0.7916 | likely_pathogenic | 0.7458 | pathogenic | -0.567 | Destabilizing | 0.722 | D | 0.586 | neutral | None | None | None | None | N |
| S/L | 0.0989 | likely_benign | 0.0809 | benign | 0.03 | Stabilizing | 0.209 | N | 0.688 | prob.neutral | None | None | None | None | N |
| S/M | 0.1627 | likely_benign | 0.1351 | benign | -0.224 | Destabilizing | 0.901 | D | 0.717 | prob.delet. | None | None | None | None | N |
| S/N | 0.2887 | likely_benign | 0.2389 | benign | -1.35 | Destabilizing | 0.888 | D | 0.61 | neutral | None | None | None | None | N |
| S/P | 0.9878 | likely_pathogenic | 0.979 | pathogenic | -0.252 | Destabilizing | 0.954 | D | 0.726 | prob.delet. | N | 0.473597284 | None | None | N |
| S/Q | 0.576 | likely_pathogenic | 0.5253 | ambiguous | -0.967 | Destabilizing | 0.965 | D | 0.65 | neutral | None | None | None | None | N |
| S/R | 0.645 | likely_pathogenic | 0.592 | pathogenic | -1.033 | Destabilizing | 0.722 | D | 0.726 | prob.delet. | None | None | None | None | N |
| S/T | 0.1131 | likely_benign | 0.0924 | benign | -0.91 | Destabilizing | 0.447 | N | 0.538 | neutral | N | 0.457064984 | None | None | N |
| S/V | 0.2069 | likely_benign | 0.1741 | benign | -0.252 | Destabilizing | 0.345 | N | 0.683 | prob.neutral | None | None | None | None | N |
| S/W | 0.2269 | likely_benign | 0.1963 | benign | -1.024 | Destabilizing | 0.901 | D | 0.726 | prob.delet. | None | None | None | None | N |
| S/Y | 0.0926 | likely_benign | 0.0832 | benign | -0.562 | Destabilizing | None | N | 0.42 | neutral | N | 0.402097135 | 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.