Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24386 | 73381;73382;73383 | chr2:178572976;178572975;178572974 | chr2:179437703;179437702;179437701 |
| N2AB | 22745 | 68458;68459;68460 | chr2:178572976;178572975;178572974 | chr2:179437703;179437702;179437701 |
| N2A | 21818 | 65677;65678;65679 | chr2:178572976;178572975;178572974 | chr2:179437703;179437702;179437701 |
| N2B | 15321 | 46186;46187;46188 | chr2:178572976;178572975;178572974 | chr2:179437703;179437702;179437701 |
| Novex-1 | 15446 | 46561;46562;46563 | chr2:178572976;178572975;178572974 | chr2:179437703;179437702;179437701 |
| Novex-2 | 15513 | 46762;46763;46764 | chr2:178572976;178572975;178572974 | chr2:179437703;179437702;179437701 |
| 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/V | rs780995546  |
-0.824 | 0.598 | N | 0.386 | 0.164 | 0.446913017954 | gnomAD-2.1.1 | 2.02E-05 | None | None | None | None | N | None | 0 | 1.16272E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66667E-04 |
| I/V | rs780995546 |
-0.824 | 0.598 | N | 0.386 | 0.164 | 0.446913017954 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 2.61883E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs780995546 |
-0.824 | 0.598 | N | 0.386 | 0.164 | 0.446913017954 | gnomAD-4.0.0 | 1.41029E-05 | None | None | None | None | N | None | 0 | 1.69532E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 2.84706E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8768 | likely_pathogenic | 0.8776 | pathogenic | -2.198 | Highly Destabilizing | 0.916 | D | 0.735 | prob.delet. | None | None | None | None | N |
| I/C | 0.923 | likely_pathogenic | 0.9258 | pathogenic | -1.84 | Destabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | N |
| I/D | 0.9973 | likely_pathogenic | 0.9966 | pathogenic | -1.754 | Destabilizing | 0.996 | D | 0.843 | deleterious | None | None | None | None | N |
| I/E | 0.9909 | likely_pathogenic | 0.989 | pathogenic | -1.488 | Destabilizing | 0.996 | D | 0.843 | deleterious | None | None | None | None | N |
| I/F | 0.4561 | ambiguous | 0.4522 | ambiguous | -1.276 | Destabilizing | 0.025 | N | 0.421 | neutral | N | 0.475180673 | None | None | N |
| I/G | 0.9907 | likely_pathogenic | 0.9901 | pathogenic | -2.765 | Highly Destabilizing | 0.987 | D | 0.837 | deleterious | None | None | None | None | N |
| I/H | 0.9843 | likely_pathogenic | 0.9808 | pathogenic | -2.182 | Highly Destabilizing | 0.999 | D | 0.831 | deleterious | None | None | None | None | N |
| I/K | 0.9753 | likely_pathogenic | 0.9702 | pathogenic | -1.617 | Destabilizing | 0.987 | D | 0.843 | deleterious | None | None | None | None | N |
| I/L | 0.1784 | likely_benign | 0.1714 | benign | -0.553 | Destabilizing | 0.426 | N | 0.397 | neutral | N | 0.489481259 | None | None | N |
| I/M | 0.2162 | likely_benign | 0.2239 | benign | -0.745 | Destabilizing | 0.983 | D | 0.702 | prob.neutral | N | 0.486211491 | None | None | N |
| I/N | 0.9776 | likely_pathogenic | 0.9735 | pathogenic | -2.042 | Highly Destabilizing | 0.994 | D | 0.834 | deleterious | N | 0.506468567 | None | None | N |
| I/P | 0.9906 | likely_pathogenic | 0.9896 | pathogenic | -1.083 | Destabilizing | 0.996 | D | 0.841 | deleterious | None | None | None | None | N |
| I/Q | 0.9811 | likely_pathogenic | 0.978 | pathogenic | -1.747 | Destabilizing | 0.999 | D | 0.853 | deleterious | None | None | None | None | N |
| I/R | 0.9654 | likely_pathogenic | 0.9599 | pathogenic | -1.622 | Destabilizing | 0.996 | D | 0.841 | deleterious | None | None | None | None | N |
| I/S | 0.9671 | likely_pathogenic | 0.964 | pathogenic | -2.863 | Highly Destabilizing | 0.983 | D | 0.793 | deleterious | N | 0.494605282 | None | None | N |
| I/T | 0.9522 | likely_pathogenic | 0.9529 | pathogenic | -2.414 | Highly Destabilizing | 0.983 | D | 0.765 | deleterious | N | 0.497821286 | None | None | N |
| I/V | 0.0765 | likely_benign | 0.0798 | benign | -1.083 | Destabilizing | 0.598 | D | 0.386 | neutral | N | 0.399670119 | None | None | N |
| I/W | 0.9824 | likely_pathogenic | 0.9776 | pathogenic | -1.49 | Destabilizing | 0.999 | D | 0.816 | deleterious | None | None | None | None | N |
| I/Y | 0.9324 | likely_pathogenic | 0.9197 | pathogenic | -1.226 | Destabilizing | 0.95 | D | 0.773 | 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.