Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25804 | 77635;77636;77637 | chr2:178568722;178568721;178568720 | chr2:179433449;179433448;179433447 |
| N2AB | 24163 | 72712;72713;72714 | chr2:178568722;178568721;178568720 | chr2:179433449;179433448;179433447 |
| N2A | 23236 | 69931;69932;69933 | chr2:178568722;178568721;178568720 | chr2:179433449;179433448;179433447 |
| N2B | 16739 | 50440;50441;50442 | chr2:178568722;178568721;178568720 | chr2:179433449;179433448;179433447 |
| Novex-1 | 16864 | 50815;50816;50817 | chr2:178568722;178568721;178568720 | chr2:179433449;179433448;179433447 |
| Novex-2 | 16931 | 51016;51017;51018 | chr2:178568722;178568721;178568720 | chr2:179433449;179433448;179433447 |
| 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/C | None | None | 0.954 | N | 0.331 | 0.352 | 0.608847247939 | gnomAD-4.0.0 | 4.80129E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.25001E-06 | 0 | 0 |
| F/L | rs536177370  |
-0.568 | None | N | 0.061 | 0.128 | 0.183819452728 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.95E-06 | 0 |
| F/L | rs536177370 |
-0.568 | None | N | 0.061 | 0.128 | 0.183819452728 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07727E-04 | 0 |
| F/L | rs536177370 |
-0.568 | None | N | 0.061 | 0.128 | 0.183819452728 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| F/L | rs536177370 |
-0.568 | None | N | 0.061 | 0.128 | 0.183819452728 | gnomAD-4.0.0 | 8.97282E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.18346E-06 | 5.36423E-05 | 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 | 0.7638 | likely_pathogenic | 0.8253 | pathogenic | -1.193 | Destabilizing | 0.007 | N | 0.169 | neutral | None | None | None | None | I |
| F/C | 0.6342 | likely_pathogenic | 0.6877 | pathogenic | -0.82 | Destabilizing | 0.954 | D | 0.331 | neutral | N | 0.501433277 | None | None | I |
| F/D | 0.9241 | likely_pathogenic | 0.9527 | pathogenic | 0.489 | Stabilizing | 0.901 | D | 0.43 | neutral | None | None | None | None | I |
| F/E | 0.944 | likely_pathogenic | 0.9615 | pathogenic | 0.512 | Stabilizing | 0.722 | D | 0.44 | neutral | None | None | None | None | I |
| F/G | 0.8622 | likely_pathogenic | 0.8998 | pathogenic | -1.388 | Destabilizing | 0.561 | D | 0.365 | neutral | None | None | None | None | I |
| F/H | 0.7864 | likely_pathogenic | 0.8294 | pathogenic | 0.119 | Stabilizing | 0.965 | D | 0.343 | neutral | None | None | None | None | I |
| F/I | 0.428 | ambiguous | 0.485 | ambiguous | -0.663 | Destabilizing | 0.166 | N | 0.249 | neutral | N | 0.499151872 | None | None | I |
| F/K | 0.9312 | likely_pathogenic | 0.9526 | pathogenic | -0.49 | Destabilizing | 0.722 | D | 0.448 | neutral | None | None | None | None | I |
| F/L | 0.9171 | likely_pathogenic | 0.9337 | pathogenic | -0.663 | Destabilizing | None | N | 0.061 | neutral | N | 0.493931782 | None | None | I |
| F/M | 0.6648 | likely_pathogenic | 0.7259 | pathogenic | -0.778 | Destabilizing | 0.103 | N | 0.155 | neutral | None | None | None | None | I |
| F/N | 0.8289 | likely_pathogenic | 0.8682 | pathogenic | -0.649 | Destabilizing | 0.965 | D | 0.404 | neutral | None | None | None | None | I |
| F/P | 0.9817 | likely_pathogenic | 0.9879 | pathogenic | -0.826 | Destabilizing | 0.901 | D | 0.415 | neutral | None | None | None | None | I |
| F/Q | 0.8955 | likely_pathogenic | 0.9202 | pathogenic | -0.599 | Destabilizing | 0.901 | D | 0.4 | neutral | None | None | None | None | I |
| F/R | 0.8767 | likely_pathogenic | 0.9032 | pathogenic | -0.099 | Destabilizing | 0.901 | D | 0.427 | neutral | None | None | None | None | I |
| F/S | 0.6698 | likely_pathogenic | 0.7513 | pathogenic | -1.307 | Destabilizing | 0.326 | N | 0.301 | neutral | N | 0.450385742 | None | None | I |
| F/T | 0.7565 | likely_pathogenic | 0.8193 | pathogenic | -1.193 | Destabilizing | 0.561 | D | 0.3 | neutral | None | None | None | None | I |
| F/V | 0.3932 | ambiguous | 0.4468 | ambiguous | -0.826 | Destabilizing | 0.005 | N | 0.119 | neutral | N | 0.510656247 | None | None | I |
| F/W | 0.6771 | likely_pathogenic | 0.7158 | pathogenic | -0.276 | Destabilizing | 0.991 | D | 0.347 | neutral | None | None | None | None | I |
| F/Y | 0.2841 | likely_benign | 0.2778 | benign | -0.391 | Destabilizing | 0.662 | D | 0.273 | neutral | N | 0.500926298 | None | None | I |
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.