Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27882 | 83869;83870;83871 | chr2:178562488;178562487;178562486 | chr2:179427215;179427214;179427213 |
| N2AB | 26241 | 78946;78947;78948 | chr2:178562488;178562487;178562486 | chr2:179427215;179427214;179427213 |
| N2A | 25314 | 76165;76166;76167 | chr2:178562488;178562487;178562486 | chr2:179427215;179427214;179427213 |
| N2B | 18817 | 56674;56675;56676 | chr2:178562488;178562487;178562486 | chr2:179427215;179427214;179427213 |
| Novex-1 | 18942 | 57049;57050;57051 | chr2:178562488;178562487;178562486 | chr2:179427215;179427214;179427213 |
| Novex-2 | 19009 | 57250;57251;57252 | chr2:178562488;178562487;178562486 | chr2:179427215;179427214;179427213 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | None | None | 0.099 | N | 0.438 | 0.057 | 0.434716162284 | gnomAD-4.0.0 | 1.59238E-06 | None | None | None | None | N | None | 0 | 2.28906E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs548211686  |
-1.08 | 0.099 | N | 0.377 | 0.045 | 0.183819452728 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.1212E-04 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs548211686 |
-1.08 | 0.099 | N | 0.377 | 0.045 | 0.183819452728 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92901E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs548211686 |
-1.08 | 0.099 | N | 0.377 | 0.045 | 0.183819452728 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| I/V | rs548211686 |
-1.08 | 0.099 | N | 0.377 | 0.045 | 0.183819452728 | gnomAD-4.0.0 | 2.47926E-06 | None | None | None | None | N | None | 1.33294E-05 | 0 | None | 0 | 6.69792E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.907 | likely_pathogenic | 0.9163 | pathogenic | -2.617 | Highly Destabilizing | 0.4 | N | 0.639 | neutral | None | None | None | None | N |
| I/C | 0.9409 | likely_pathogenic | 0.9416 | pathogenic | -1.449 | Destabilizing | 0.992 | D | 0.739 | prob.delet. | None | None | None | None | N |
| I/D | 0.999 | likely_pathogenic | 0.9992 | pathogenic | -3.042 | Highly Destabilizing | 0.972 | D | 0.813 | deleterious | None | None | None | None | N |
| I/E | 0.9963 | likely_pathogenic | 0.9971 | pathogenic | -2.698 | Highly Destabilizing | 0.92 | D | 0.775 | deleterious | None | None | None | None | N |
| I/F | 0.4353 | ambiguous | 0.4482 | ambiguous | -1.503 | Destabilizing | 0.379 | N | 0.683 | prob.neutral | N | 0.468783487 | None | None | N |
| I/G | 0.9893 | likely_pathogenic | 0.991 | pathogenic | -3.241 | Highly Destabilizing | 0.92 | D | 0.771 | deleterious | None | None | None | None | N |
| I/H | 0.9943 | likely_pathogenic | 0.9953 | pathogenic | -3.007 | Highly Destabilizing | 0.992 | D | 0.826 | deleterious | None | None | None | None | N |
| I/K | 0.9932 | likely_pathogenic | 0.9947 | pathogenic | -1.712 | Destabilizing | 0.85 | D | 0.772 | deleterious | None | None | None | None | N |
| I/L | 0.0838 | likely_benign | 0.0902 | benign | -0.725 | Destabilizing | 0.001 | N | 0.227 | neutral | N | 0.29145407 | None | None | N |
| I/M | 0.177 | likely_benign | 0.1863 | benign | -0.885 | Destabilizing | 0.099 | N | 0.438 | neutral | N | 0.479096481 | None | None | N |
| I/N | 0.9906 | likely_pathogenic | 0.9924 | pathogenic | -2.475 | Highly Destabilizing | 0.896 | D | 0.817 | deleterious | N | 0.478561261 | None | None | N |
| I/P | 0.9944 | likely_pathogenic | 0.9954 | pathogenic | -1.349 | Destabilizing | 0.972 | D | 0.814 | deleterious | None | None | None | None | N |
| I/Q | 0.9918 | likely_pathogenic | 0.9936 | pathogenic | -2.038 | Highly Destabilizing | 0.92 | D | 0.815 | deleterious | None | None | None | None | N |
| I/R | 0.9885 | likely_pathogenic | 0.9911 | pathogenic | -1.997 | Destabilizing | 0.85 | D | 0.806 | deleterious | None | None | None | None | N |
| I/S | 0.9801 | likely_pathogenic | 0.9832 | pathogenic | -2.981 | Highly Destabilizing | 0.549 | D | 0.705 | prob.neutral | N | 0.478307772 | None | None | N |
| I/T | 0.9584 | likely_pathogenic | 0.9621 | pathogenic | -2.463 | Highly Destabilizing | 0.549 | D | 0.625 | neutral | N | 0.466786882 | None | None | N |
| I/V | 0.0998 | likely_benign | 0.0984 | benign | -1.349 | Destabilizing | 0.099 | N | 0.377 | neutral | N | 0.411364406 | None | None | N |
| I/W | 0.9759 | likely_pathogenic | 0.9818 | pathogenic | -1.808 | Destabilizing | 0.992 | D | 0.824 | deleterious | None | None | None | None | N |
| I/Y | 0.9429 | likely_pathogenic | 0.9513 | pathogenic | -1.645 | Destabilizing | 0.92 | D | 0.72 | prob.delet. | 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.