Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23900 | 71923;71924;71925 | chr2:178574434;178574433;178574432 | chr2:179439161;179439160;179439159 |
| N2AB | 22259 | 67000;67001;67002 | chr2:178574434;178574433;178574432 | chr2:179439161;179439160;179439159 |
| N2A | 21332 | 64219;64220;64221 | chr2:178574434;178574433;178574432 | chr2:179439161;179439160;179439159 |
| N2B | 14835 | 44728;44729;44730 | chr2:178574434;178574433;178574432 | chr2:179439161;179439160;179439159 |
| Novex-1 | 14960 | 45103;45104;45105 | chr2:178574434;178574433;178574432 | chr2:179439161;179439160;179439159 |
| Novex-2 | 15027 | 45304;45305;45306 | chr2:178574434;178574433;178574432 | chr2:179439161;179439160;179439159 |
| 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/P | None | None | 1.0 | D | 0.805 | 0.683 | 0.680650368104 | gnomAD-4.0.0 | 6.84325E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99593E-07 | 0 | 0 |
| R/Q | rs369292052  |
-0.912 | 1.0 | N | 0.787 | 0.612 | None | gnomAD-2.1.1 | 2.86E-05 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 3.13E-05 | 0 |
| R/Q | rs369292052 |
-0.912 | 1.0 | N | 0.787 | 0.612 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 1.93424E-04 | None | 0 | 0 | 5.88E-05 | 0 | 4.79386E-04 |
| R/Q | rs369292052 |
-0.912 | 1.0 | N | 0.787 | 0.612 | None | gnomAD-4.0.0 | 5.08248E-05 | None | None | None | None | N | None | 5.34088E-05 | 0 | None | 0 | 2.22906E-05 | None | 0 | 0 | 5.84941E-05 | 7.6869E-05 | 1.60149E-05 |
| R/W | rs755894115 |
-0.687 | 1.0 | D | 0.801 | 0.663 | 0.775599910008 | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | N | None | 4.13E-05 | 5.66E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| R/W | rs755894115 |
-0.687 | 1.0 | D | 0.801 | 0.663 | 0.775599910008 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/W | rs755894115 |
-0.687 | 1.0 | D | 0.801 | 0.663 | 0.775599910008 | gnomAD-4.0.0 | 6.19835E-06 | None | None | None | None | N | None | 1.33561E-05 | 1.66739E-05 | None | 0 | 2.22926E-05 | None | 0 | 0 | 3.391E-06 | 1.09825E-05 | 3.20287E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.937 | likely_pathogenic | 0.9391 | pathogenic | -2.036 | Highly Destabilizing | 0.999 | D | 0.629 | neutral | None | None | None | None | N |
| R/C | 0.3518 | ambiguous | 0.4073 | ambiguous | -1.915 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| R/D | 0.9949 | likely_pathogenic | 0.9951 | pathogenic | -1.143 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| R/E | 0.9147 | likely_pathogenic | 0.9273 | pathogenic | -0.913 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | N |
| R/F | 0.9619 | likely_pathogenic | 0.9682 | pathogenic | -1.144 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| R/G | 0.9333 | likely_pathogenic | 0.9414 | pathogenic | -2.381 | Highly Destabilizing | 1.0 | D | 0.735 | prob.delet. | D | 0.561884195 | None | None | N |
| R/H | 0.3214 | likely_benign | 0.3424 | ambiguous | -2.146 | Highly Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| R/I | 0.8633 | likely_pathogenic | 0.8846 | pathogenic | -1.022 | Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | N |
| R/K | 0.2963 | likely_benign | 0.3396 | benign | -1.28 | Destabilizing | 0.998 | D | 0.653 | neutral | None | None | None | None | N |
| R/L | 0.7897 | likely_pathogenic | 0.8201 | pathogenic | -1.022 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | N | 0.516547879 | None | None | N |
| R/M | 0.8439 | likely_pathogenic | 0.8755 | pathogenic | -1.569 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| R/N | 0.9746 | likely_pathogenic | 0.9778 | pathogenic | -1.45 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| R/P | 0.9981 | likely_pathogenic | 0.9982 | pathogenic | -1.351 | Destabilizing | 1.0 | D | 0.805 | deleterious | D | 0.562391174 | None | None | N |
| R/Q | 0.2426 | likely_benign | 0.2706 | benign | -1.235 | Destabilizing | 1.0 | D | 0.787 | deleterious | N | 0.50817686 | None | None | N |
| R/S | 0.9505 | likely_pathogenic | 0.9592 | pathogenic | -2.278 | Highly Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| R/T | 0.9088 | likely_pathogenic | 0.9251 | pathogenic | -1.834 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| R/V | 0.8825 | likely_pathogenic | 0.8999 | pathogenic | -1.351 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| R/W | 0.6818 | likely_pathogenic | 0.7285 | pathogenic | -0.691 | Destabilizing | 1.0 | D | 0.801 | deleterious | D | 0.550781379 | None | None | N |
| R/Y | 0.8918 | likely_pathogenic | 0.9075 | pathogenic | -0.577 | Destabilizing | 1.0 | D | 0.833 | 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.