Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18035 | 54328;54329;54330 | chr2:178605074;178605073;178605072 | chr2:179469801;179469800;179469799 |
| N2AB | 16394 | 49405;49406;49407 | chr2:178605074;178605073;178605072 | chr2:179469801;179469800;179469799 |
| N2A | 15467 | 46624;46625;46626 | chr2:178605074;178605073;178605072 | chr2:179469801;179469800;179469799 |
| N2B | 8970 | 27133;27134;27135 | chr2:178605074;178605073;178605072 | chr2:179469801;179469800;179469799 |
| Novex-1 | 9095 | 27508;27509;27510 | chr2:178605074;178605073;178605072 | chr2:179469801;179469800;179469799 |
| Novex-2 | 9162 | 27709;27710;27711 | chr2:178605074;178605073;178605072 | chr2:179469801;179469800;179469799 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/V | rs182445366  |
-0.464 | 0.009 | N | 0.285 | 0.111 | None | gnomAD-2.1.1 | 4.3E-05 | None | None | None | None | N | None | 0 | 5.66E-05 | None | 1.94401E-04 | 0 | None | 0 | None | 4.01E-05 | 2.36E-05 | 5.63222E-04 |
| A/V | rs182445366 |
-0.464 | 0.009 | N | 0.285 | 0.111 | None | gnomAD-3.1.2 | 1.57992E-04 | None | None | None | None | N | None | 7.24E-05 | 9.85416E-04 | 0 | 0 | 0 | None | 0 | 0 | 5.89E-05 | 0 | 9.56023E-04 |
| A/V | rs182445366 |
-0.464 | 0.009 | N | 0.285 | 0.111 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| A/V | rs182445366 |
-0.464 | 0.009 | N | 0.285 | 0.111 | None | gnomAD-4.0.0 | 4.03078E-05 | None | None | None | None | N | None | 5.33789E-05 | 3.33712E-04 | None | 3.04486E-04 | 0 | None | 0 | 0 | 1.61138E-05 | 2.1978E-05 | 1.76203E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5442 | ambiguous | 0.5781 | pathogenic | -1.356 | Destabilizing | 0.947 | D | 0.679 | prob.neutral | None | None | None | None | N |
| A/D | 0.9855 | likely_pathogenic | 0.9815 | pathogenic | -2.271 | Highly Destabilizing | 0.539 | D | 0.749 | deleterious | None | None | None | None | N |
| A/E | 0.9776 | likely_pathogenic | 0.9709 | pathogenic | -2.257 | Highly Destabilizing | 0.691 | D | 0.738 | prob.delet. | N | 0.513794807 | None | None | N |
| A/F | 0.9484 | likely_pathogenic | 0.9462 | pathogenic | -1.192 | Destabilizing | 0.7 | D | 0.733 | prob.delet. | None | None | None | None | N |
| A/G | 0.4024 | ambiguous | 0.364 | ambiguous | -1.492 | Destabilizing | 0.39 | N | 0.526 | neutral | D | 0.532120969 | None | None | N |
| A/H | 0.9851 | likely_pathogenic | 0.9823 | pathogenic | -1.571 | Destabilizing | 0.947 | D | 0.736 | prob.delet. | None | None | None | None | N |
| A/I | 0.5076 | ambiguous | 0.5147 | ambiguous | -0.563 | Destabilizing | 0.103 | N | 0.675 | prob.neutral | None | None | None | None | N |
| A/K | 0.9931 | likely_pathogenic | 0.9911 | pathogenic | -1.468 | Destabilizing | 0.539 | D | 0.733 | prob.delet. | None | None | None | None | N |
| A/L | 0.5931 | likely_pathogenic | 0.5987 | pathogenic | -0.563 | Destabilizing | 0.25 | N | 0.569 | neutral | None | None | None | None | N |
| A/M | 0.6452 | likely_pathogenic | 0.6456 | pathogenic | -0.577 | Destabilizing | 0.898 | D | 0.726 | prob.delet. | None | None | None | None | N |
| A/N | 0.9233 | likely_pathogenic | 0.9111 | pathogenic | -1.411 | Destabilizing | 0.539 | D | 0.752 | deleterious | None | None | None | None | N |
| A/P | 0.7976 | likely_pathogenic | 0.7841 | pathogenic | -0.74 | Destabilizing | 0.638 | D | 0.757 | deleterious | N | 0.490004987 | None | None | N |
| A/Q | 0.9708 | likely_pathogenic | 0.9635 | pathogenic | -1.569 | Destabilizing | 0.7 | D | 0.727 | prob.delet. | None | None | None | None | N |
| A/R | 0.9853 | likely_pathogenic | 0.9804 | pathogenic | -1.108 | Destabilizing | 0.7 | D | 0.737 | prob.delet. | None | None | None | None | N |
| A/S | 0.1854 | likely_benign | 0.1748 | benign | -1.713 | Destabilizing | 0.004 | N | 0.353 | neutral | N | 0.461298233 | None | None | N |
| A/T | 0.148 | likely_benign | 0.1465 | benign | -1.619 | Destabilizing | 0.201 | N | 0.56 | neutral | N | 0.452948109 | None | None | N |
| A/V | 0.1938 | likely_benign | 0.1968 | benign | -0.74 | Destabilizing | 0.009 | N | 0.285 | neutral | N | 0.400396129 | None | None | N |
| A/W | 0.9941 | likely_pathogenic | 0.9936 | pathogenic | -1.596 | Destabilizing | 0.982 | D | 0.736 | prob.delet. | None | None | None | None | N |
| A/Y | 0.979 | likely_pathogenic | 0.9771 | pathogenic | -1.199 | Destabilizing | 0.826 | D | 0.747 | deleterious | 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.