Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29395 | 88408;88409;88410 | chr2:178556971;178556970;178556969 | chr2:179421698;179421697;179421696 |
| N2AB | 27754 | 83485;83486;83487 | chr2:178556971;178556970;178556969 | chr2:179421698;179421697;179421696 |
| N2A | 26827 | 80704;80705;80706 | chr2:178556971;178556970;178556969 | chr2:179421698;179421697;179421696 |
| N2B | 20330 | 61213;61214;61215 | chr2:178556971;178556970;178556969 | chr2:179421698;179421697;179421696 |
| Novex-1 | 20455 | 61588;61589;61590 | chr2:178556971;178556970;178556969 | chr2:179421698;179421697;179421696 |
| Novex-2 | 20522 | 61789;61790;61791 | chr2:178556971;178556970;178556969 | chr2:179421698;179421697;179421696 |
| 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 | rs55940667  |
-0.97 | 0.008 | N | 0.287 | 0.219 | 0.226586394389 | gnomAD-2.1.1 | 1.39264E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.90604E-03 | None | 6.54E-05 | None | 0 | 0 | 0 |
| F/L | rs55940667 |
-0.97 | 0.008 | N | 0.287 | 0.219 | 0.226586394389 | gnomAD-3.1.2 | 9.86E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 2.69749E-03 | None | 0 | 0 | 0 | 2.06954E-04 | 0 |
| F/L | rs55940667 |
-0.97 | 0.008 | N | 0.287 | 0.219 | 0.226586394389 | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 2E-03 | 0 | None | None | None | 0 | None |
| F/L | rs55940667 |
-0.97 | 0.008 | N | 0.287 | 0.219 | 0.226586394389 | gnomAD-4.0.0 | 3.65591E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.0492E-03 | None | 0 | 0 | 0 | 4.39174E-05 | 1.28057E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.8698 | likely_pathogenic | 0.7878 | pathogenic | -1.951 | Destabilizing | 0.775 | D | 0.577 | neutral | None | None | None | None | N |
| F/C | 0.4812 | ambiguous | 0.374 | ambiguous | -1.308 | Destabilizing | 0.995 | D | 0.714 | prob.delet. | N | 0.489390833 | None | None | N |
| F/D | 0.9662 | likely_pathogenic | 0.9442 | pathogenic | -1.289 | Destabilizing | 0.987 | D | 0.737 | prob.delet. | None | None | None | None | N |
| F/E | 0.9664 | likely_pathogenic | 0.9438 | pathogenic | -1.113 | Destabilizing | 0.961 | D | 0.723 | prob.delet. | None | None | None | None | N |
| F/G | 0.9198 | likely_pathogenic | 0.8764 | pathogenic | -2.34 | Highly Destabilizing | 0.961 | D | 0.646 | neutral | None | None | None | None | N |
| F/H | 0.7708 | likely_pathogenic | 0.6861 | pathogenic | -0.629 | Destabilizing | 0.923 | D | 0.667 | neutral | None | None | None | None | N |
| F/I | 0.6118 | likely_pathogenic | 0.4592 | ambiguous | -0.737 | Destabilizing | 0.565 | D | 0.404 | neutral | N | 0.474749373 | None | None | N |
| F/K | 0.9661 | likely_pathogenic | 0.9414 | pathogenic | -1.509 | Destabilizing | 0.961 | D | 0.719 | prob.delet. | None | None | None | None | N |
| F/L | 0.9275 | likely_pathogenic | 0.8682 | pathogenic | -0.737 | Destabilizing | 0.008 | N | 0.287 | neutral | N | 0.508051164 | None | None | N |
| F/M | 0.7178 | likely_pathogenic | 0.604 | pathogenic | -0.618 | Destabilizing | 0.923 | D | 0.481 | neutral | None | None | None | None | N |
| F/N | 0.9037 | likely_pathogenic | 0.8463 | pathogenic | -1.922 | Destabilizing | 0.987 | D | 0.741 | deleterious | None | None | None | None | N |
| F/P | 0.9994 | likely_pathogenic | 0.9988 | pathogenic | -1.142 | Destabilizing | 0.987 | D | 0.746 | deleterious | None | None | None | None | N |
| F/Q | 0.933 | likely_pathogenic | 0.8927 | pathogenic | -1.801 | Destabilizing | 0.987 | D | 0.747 | deleterious | None | None | None | None | N |
| F/R | 0.9315 | likely_pathogenic | 0.8867 | pathogenic | -1.115 | Destabilizing | 0.961 | D | 0.739 | prob.delet. | None | None | None | None | N |
| F/S | 0.8413 | likely_pathogenic | 0.7513 | pathogenic | -2.648 | Highly Destabilizing | 0.949 | D | 0.606 | neutral | N | 0.502528093 | None | None | N |
| F/T | 0.8911 | likely_pathogenic | 0.8161 | pathogenic | -2.367 | Highly Destabilizing | 0.923 | D | 0.611 | neutral | None | None | None | None | N |
| F/V | 0.5613 | ambiguous | 0.4159 | ambiguous | -1.142 | Destabilizing | 0.565 | D | 0.517 | neutral | N | 0.464728832 | None | None | N |
| F/W | 0.7288 | likely_pathogenic | 0.6419 | pathogenic | 0.254 | Stabilizing | 0.996 | D | 0.477 | neutral | None | None | None | None | N |
| F/Y | 0.151 | likely_benign | 0.1274 | benign | -0.078 | Destabilizing | 0.034 | N | 0.36 | neutral | N | 0.453080529 | 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.