Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29411 | 88456;88457;88458 | chr2:178556923;178556922;178556921 | chr2:179421650;179421649;179421648 |
| N2AB | 27770 | 83533;83534;83535 | chr2:178556923;178556922;178556921 | chr2:179421650;179421649;179421648 |
| N2A | 26843 | 80752;80753;80754 | chr2:178556923;178556922;178556921 | chr2:179421650;179421649;179421648 |
| N2B | 20346 | 61261;61262;61263 | chr2:178556923;178556922;178556921 | chr2:179421650;179421649;179421648 |
| Novex-1 | 20471 | 61636;61637;61638 | chr2:178556923;178556922;178556921 | chr2:179421650;179421649;179421648 |
| Novex-2 | 20538 | 61837;61838;61839 | chr2:178556923;178556922;178556921 | chr2:179421650;179421649;179421648 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs1701736067  |
None | 0.001 | N | 0.228 | 0.255 | 0.234412748748 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| F/L | rs1701736067 |
None | 0.001 | N | 0.228 | 0.255 | 0.234412748748 | gnomAD-4.0.0 | 6.57056E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46998E-05 | 0 | 0 |
| F/Y | rs1433228812 |
-1.376 | 0.662 | N | 0.583 | 0.157 | 0.454145904683 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.6E-05 | None | 0 | None | 0 | 0 | 0 |
| F/Y | rs1433228812 |
-1.376 | 0.662 | N | 0.583 | 0.157 | 0.454145904683 | gnomAD-4.0.0 | 1.59127E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77886E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.5175 | ambiguous | 0.4454 | ambiguous | -3.445 | Highly Destabilizing | 0.345 | N | 0.706 | prob.neutral | None | None | None | None | N |
| F/C | 0.2727 | likely_benign | 0.2183 | benign | -1.993 | Destabilizing | 0.987 | D | 0.727 | prob.delet. | N | 0.464473746 | None | None | N |
| F/D | 0.9442 | likely_pathogenic | 0.9307 | pathogenic | -3.556 | Highly Destabilizing | 0.901 | D | 0.781 | deleterious | None | None | None | None | N |
| F/E | 0.9246 | likely_pathogenic | 0.9093 | pathogenic | -3.404 | Highly Destabilizing | 0.561 | D | 0.739 | prob.delet. | None | None | None | None | N |
| F/G | 0.8452 | likely_pathogenic | 0.7999 | pathogenic | -3.813 | Highly Destabilizing | 0.722 | D | 0.731 | prob.delet. | None | None | None | None | N |
| F/H | 0.6109 | likely_pathogenic | 0.5592 | ambiguous | -2.103 | Highly Destabilizing | 0.965 | D | 0.745 | deleterious | None | None | None | None | N |
| F/I | 0.1881 | likely_benign | 0.1516 | benign | -2.234 | Highly Destabilizing | 0.013 | N | 0.269 | neutral | N | 0.386839681 | None | None | N |
| F/K | 0.8277 | likely_pathogenic | 0.8061 | pathogenic | -2.313 | Highly Destabilizing | 0.017 | N | 0.608 | neutral | None | None | None | None | N |
| F/L | 0.7171 | likely_pathogenic | 0.6749 | pathogenic | -2.234 | Highly Destabilizing | 0.001 | N | 0.228 | neutral | N | 0.437844505 | None | None | N |
| F/M | 0.3768 | ambiguous | 0.3491 | ambiguous | -1.81 | Destabilizing | 0.047 | N | 0.281 | neutral | None | None | None | None | N |
| F/N | 0.7809 | likely_pathogenic | 0.7514 | pathogenic | -2.595 | Highly Destabilizing | 0.901 | D | 0.779 | deleterious | None | None | None | None | N |
| F/P | 0.9975 | likely_pathogenic | 0.9974 | pathogenic | -2.649 | Highly Destabilizing | 0.965 | D | 0.778 | deleterious | None | None | None | None | N |
| F/Q | 0.7497 | likely_pathogenic | 0.7177 | pathogenic | -2.703 | Highly Destabilizing | 0.818 | D | 0.78 | deleterious | None | None | None | None | N |
| F/R | 0.6931 | likely_pathogenic | 0.6471 | pathogenic | -1.514 | Destabilizing | 0.39 | N | 0.773 | deleterious | None | None | None | None | N |
| F/S | 0.4236 | ambiguous | 0.3438 | ambiguous | -3.22 | Highly Destabilizing | 0.491 | N | 0.733 | prob.delet. | N | 0.41754659 | None | None | N |
| F/T | 0.431 | ambiguous | 0.3551 | ambiguous | -2.981 | Highly Destabilizing | 0.561 | D | 0.735 | prob.delet. | None | None | None | None | N |
| F/V | 0.2208 | likely_benign | 0.1804 | benign | -2.649 | Highly Destabilizing | 0.08 | N | 0.629 | neutral | N | 0.431302534 | None | None | N |
| F/W | 0.5571 | ambiguous | 0.4839 | ambiguous | -0.968 | Destabilizing | 0.991 | D | 0.691 | prob.neutral | None | None | None | None | N |
| F/Y | 0.1899 | likely_benign | 0.1928 | benign | -1.39 | Destabilizing | 0.662 | D | 0.583 | neutral | N | 0.468916773 | 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.