Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24621 | 74086;74087;74088 | chr2:178572271;178572270;178572269 | chr2:179436998;179436997;179436996 |
| N2AB | 22980 | 69163;69164;69165 | chr2:178572271;178572270;178572269 | chr2:179436998;179436997;179436996 |
| N2A | 22053 | 66382;66383;66384 | chr2:178572271;178572270;178572269 | chr2:179436998;179436997;179436996 |
| N2B | 15556 | 46891;46892;46893 | chr2:178572271;178572270;178572269 | chr2:179436998;179436997;179436996 |
| Novex-1 | 15681 | 47266;47267;47268 | chr2:178572271;178572270;178572269 | chr2:179436998;179436997;179436996 |
| Novex-2 | 15748 | 47467;47468;47469 | chr2:178572271;178572270;178572269 | chr2:179436998;179436997;179436996 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/R | rs776476061  |
-1.114 | 1.0 | N | 0.784 | 0.336 | 0.5732715451 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.61E-05 | None | 3.27E-05 | None | 0 | 0 | 0 |
| G/R | rs776476061 |
-1.114 | 1.0 | N | 0.784 | 0.336 | 0.5732715451 |
Huang (2021)
| None |
Other 
|
comp het with Y4418* | None | None | N | Genetic analysis of NMD patients; variant prioritisation; no validation | None | None | None | None | None | None | None | None | None | None | None |
| G/R | rs776476061 |
-1.114 | 1.0 | N | 0.784 | 0.336 | 0.5732715451 | gnomAD-4.0.0 | 7.5294E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52666E-05 | None | 0 | 0 | 0 | 1.04408E-04 | 1.65739E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.2126 | likely_benign | 0.2051 | benign | -0.836 | Destabilizing | 1.0 | D | 0.644 | neutral | N | 0.477218135 | None | None | N |
| G/C | 0.4444 | ambiguous | 0.4313 | ambiguous | -1.018 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| G/D | 0.7453 | likely_pathogenic | 0.7233 | pathogenic | -2.01 | Highly Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| G/E | 0.5823 | likely_pathogenic | 0.5569 | ambiguous | -1.97 | Destabilizing | 1.0 | D | 0.8 | deleterious | N | 0.468922795 | None | None | N |
| G/F | 0.8833 | likely_pathogenic | 0.8685 | pathogenic | -0.919 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| G/H | 0.7778 | likely_pathogenic | 0.767 | pathogenic | -1.799 | Destabilizing | 1.0 | D | 0.766 | deleterious | None | None | None | None | N |
| G/I | 0.7129 | likely_pathogenic | 0.6851 | pathogenic | -0.146 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| G/K | 0.7377 | likely_pathogenic | 0.737 | pathogenic | -1.587 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| G/L | 0.7054 | likely_pathogenic | 0.6707 | pathogenic | -0.146 | Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | N |
| G/M | 0.7414 | likely_pathogenic | 0.7233 | pathogenic | -0.166 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| G/N | 0.6346 | likely_pathogenic | 0.6196 | pathogenic | -1.435 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| G/P | 0.9762 | likely_pathogenic | 0.9751 | pathogenic | -0.333 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| G/Q | 0.5744 | likely_pathogenic | 0.5499 | ambiguous | -1.481 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| G/R | 0.5588 | ambiguous | 0.559 | ambiguous | -1.378 | Destabilizing | 1.0 | D | 0.784 | deleterious | N | 0.466872106 | None | None | N |
| G/S | 0.1759 | likely_benign | 0.1607 | benign | -1.66 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| G/T | 0.4063 | ambiguous | 0.3876 | ambiguous | -1.541 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | N |
| G/V | 0.5116 | ambiguous | 0.4768 | ambiguous | -0.333 | Destabilizing | 1.0 | D | 0.793 | deleterious | N | 0.478890429 | None | None | N |
| G/W | 0.8251 | likely_pathogenic | 0.7994 | pathogenic | -1.542 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| G/Y | 0.8129 | likely_pathogenic | 0.797 | pathogenic | -1.048 | Destabilizing | 1.0 | D | 0.772 | 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.