Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28624 | 86095;86096;86097 | chr2:178560262;178560261;178560260 | chr2:179424989;179424988;179424987 |
| N2AB | 26983 | 81172;81173;81174 | chr2:178560262;178560261;178560260 | chr2:179424989;179424988;179424987 |
| N2A | 26056 | 78391;78392;78393 | chr2:178560262;178560261;178560260 | chr2:179424989;179424988;179424987 |
| N2B | 19559 | 58900;58901;58902 | chr2:178560262;178560261;178560260 | chr2:179424989;179424988;179424987 |
| Novex-1 | 19684 | 59275;59276;59277 | chr2:178560262;178560261;178560260 | chr2:179424989;179424988;179424987 |
| Novex-2 | 19751 | 59476;59477;59478 | chr2:178560262;178560261;178560260 | chr2:179424989;179424988;179424987 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs398124458  |
-1.646 | 0.996 | D | 0.741 | 0.466 | 0.624694708293 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 8.87E-06 | 0 |
| R/C | rs398124458 |
-1.646 | 0.996 | D | 0.741 | 0.466 | 0.624694708293 | gnomAD-4.0.0 | 4.10519E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52042E-05 | None | 0 | 0 | 4.4973E-06 | 0 | 0 |
| R/H | rs538641703 |
-2.255 | 0.908 | D | 0.58 | 0.402 | 0.253726318573 | gnomAD-2.1.1 | 1.14181E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.15092E-04 | None | 7.99E-05 | 7.8E-06 | 1.40331E-04 |
| R/H | rs538641703 |
-2.255 | 0.908 | D | 0.58 | 0.402 | 0.253726318573 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 8.28157E-04 | 0 |
| R/H | rs538641703 |
-2.255 | 0.908 | D | 0.58 | 0.402 | 0.253726318573 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| R/H | rs538641703 |
-2.255 | 0.908 | D | 0.58 | 0.402 | 0.253726318573 | gnomAD-4.0.0 | 7.37399E-05 | None | None | None | None | N | None | 1.33316E-05 | 1.66656E-05 | None | 0 | 0 | None | 7.81177E-05 | 1.65071E-04 | 3.39044E-05 | 7.79517E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8333 | likely_pathogenic | 0.7533 | pathogenic | -2.045 | Highly Destabilizing | 0.25 | N | 0.543 | neutral | None | None | None | None | N |
| R/C | 0.2695 | likely_benign | 0.1989 | benign | -1.871 | Destabilizing | 0.996 | D | 0.741 | deleterious | D | 0.538108401 | None | None | N |
| R/D | 0.9848 | likely_pathogenic | 0.9708 | pathogenic | -1.051 | Destabilizing | 0.7 | D | 0.575 | neutral | None | None | None | None | N |
| R/E | 0.8182 | likely_pathogenic | 0.7394 | pathogenic | -0.819 | Destabilizing | 0.25 | N | 0.563 | neutral | None | None | None | None | N |
| R/F | 0.8827 | likely_pathogenic | 0.8121 | pathogenic | -1.184 | Destabilizing | 0.935 | D | 0.761 | deleterious | None | None | None | None | N |
| R/G | 0.8375 | likely_pathogenic | 0.7567 | pathogenic | -2.397 | Highly Destabilizing | 0.561 | D | 0.553 | neutral | D | 0.552832068 | None | None | N |
| R/H | 0.1703 | likely_benign | 0.1256 | benign | -2.067 | Highly Destabilizing | 0.908 | D | 0.58 | neutral | D | 0.541729252 | None | None | N |
| R/I | 0.6845 | likely_pathogenic | 0.5865 | pathogenic | -1.014 | Destabilizing | 0.826 | D | 0.743 | deleterious | None | None | None | None | N |
| R/K | 0.2399 | likely_benign | 0.2099 | benign | -1.153 | Destabilizing | 0.121 | N | 0.619 | neutral | None | None | None | None | N |
| R/L | 0.6034 | likely_pathogenic | 0.5193 | ambiguous | -1.014 | Destabilizing | 0.561 | D | 0.553 | neutral | D | 0.522308324 | None | None | N |
| R/M | 0.6727 | likely_pathogenic | 0.5723 | pathogenic | -1.535 | Destabilizing | 0.947 | D | 0.627 | neutral | None | None | None | None | N |
| R/N | 0.9296 | likely_pathogenic | 0.8776 | pathogenic | -1.335 | Destabilizing | 0.7 | D | 0.52 | neutral | None | None | None | None | N |
| R/P | 0.9969 | likely_pathogenic | 0.9947 | pathogenic | -1.348 | Destabilizing | 0.901 | D | 0.65 | neutral | D | 0.564859936 | None | None | N |
| R/Q | 0.1681 | likely_benign | 0.1389 | benign | -1.168 | Destabilizing | 0.005 | N | 0.453 | neutral | None | None | None | None | N |
| R/S | 0.8811 | likely_pathogenic | 0.8117 | pathogenic | -2.227 | Highly Destabilizing | 0.39 | N | 0.527 | neutral | N | 0.51875947 | None | None | N |
| R/T | 0.7507 | likely_pathogenic | 0.6535 | pathogenic | -1.776 | Destabilizing | 0.7 | D | 0.521 | neutral | None | None | None | None | N |
| R/V | 0.7264 | likely_pathogenic | 0.6356 | pathogenic | -1.348 | Destabilizing | 0.7 | D | 0.707 | prob.neutral | None | None | None | None | N |
| R/W | 0.4708 | ambiguous | 0.3695 | ambiguous | -0.683 | Destabilizing | 0.982 | D | 0.713 | prob.delet. | None | None | None | None | N |
| R/Y | 0.7774 | likely_pathogenic | 0.673 | pathogenic | -0.572 | Destabilizing | 0.826 | D | 0.691 | prob.neutral | 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.