Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25641 | 77146;77147;77148 | chr2:178569211;178569210;178569209 | chr2:179433938;179433937;179433936 |
| N2AB | 24000 | 72223;72224;72225 | chr2:178569211;178569210;178569209 | chr2:179433938;179433937;179433936 |
| N2A | 23073 | 69442;69443;69444 | chr2:178569211;178569210;178569209 | chr2:179433938;179433937;179433936 |
| N2B | 16576 | 49951;49952;49953 | chr2:178569211;178569210;178569209 | chr2:179433938;179433937;179433936 |
| Novex-1 | 16701 | 50326;50327;50328 | chr2:178569211;178569210;178569209 | chr2:179433938;179433937;179433936 |
| Novex-2 | 16768 | 50527;50528;50529 | chr2:178569211;178569210;178569209 | chr2:179433938;179433937;179433936 |
| 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 | rs549745098  |
-1.903 | 1.0 | N | 0.782 | 0.473 | 0.670176712172 | gnomAD-2.1.1 | 2.05E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.23864E-04 | None | 0 | None | 0 | 9E-06 | 0 |
| R/C | rs549745098 |
-1.903 | 1.0 | N | 0.782 | 0.473 | 0.670176712172 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93424E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs549745098 |
-1.903 | 1.0 | N | 0.782 | 0.473 | 0.670176712172 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/C | rs549745098 |
-1.903 | 1.0 | N | 0.782 | 0.473 | 0.670176712172 | gnomAD-4.0.0 | 6.84366E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 8.93296E-05 | None | 0 | 0 | 5.94943E-06 | 0 | 0 |
| R/H | rs369707906 |
-2.602 | 0.999 | N | 0.569 | 0.45 | None | gnomAD-2.1.1 | 6.31795E-04 | None | None | None | None | N | None | 4.15E-05 | 0 | None | 0 | 0 | None | 5.74398E-03 | None | 0 | 3.17E-05 | 1.43802E-04 |
| R/H | rs369707906 |
-2.602 | 0.999 | N | 0.569 | 0.45 | None | gnomAD-3.1.2 | 2.89348E-04 | None | None | None | None | N | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 7.45033E-03 | 0 |
| R/H | rs369707906 |
-2.602 | 0.999 | N | 0.569 | 0.45 | None | 1000 genomes | 1.99681E-03 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1.02E-02 | None |
| R/H | rs369707906 |
-2.602 | 0.999 | N | 0.569 | 0.45 | None | gnomAD-4.0.0 | 4.96591E-04 | None | None | None | None | N | None | 1.20588E-04 | 0 | None | 0 | 0 | None | 0 | 1.66168E-04 | 2.02316E-04 | 5.84711E-03 | 4.02188E-04 |
| R/L | None | None | 0.996 | N | 0.679 | 0.454 | 0.681492719615 | gnomAD-4.0.0 | 6.87392E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87913E-05 | 0 | 0 | 0 | 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 | 0.9833 | likely_pathogenic | 0.9823 | pathogenic | -2.227 | Highly Destabilizing | 0.961 | D | 0.552 | neutral | None | None | None | None | N |
| R/C | 0.6887 | likely_pathogenic | 0.6944 | pathogenic | -2.005 | Highly Destabilizing | 1.0 | D | 0.782 | deleterious | N | 0.492768403 | None | None | N |
| R/D | 0.9987 | likely_pathogenic | 0.9986 | pathogenic | -0.897 | Destabilizing | 0.994 | D | 0.679 | prob.neutral | None | None | None | None | N |
| R/E | 0.9844 | likely_pathogenic | 0.9812 | pathogenic | -0.687 | Destabilizing | 0.968 | D | 0.517 | neutral | None | None | None | None | N |
| R/F | 0.9863 | likely_pathogenic | 0.9887 | pathogenic | -1.523 | Destabilizing | 0.998 | D | 0.8 | deleterious | None | None | None | None | N |
| R/G | 0.9709 | likely_pathogenic | 0.9708 | pathogenic | -2.561 | Highly Destabilizing | 0.229 | N | 0.411 | neutral | N | 0.507656654 | None | None | N |
| R/H | 0.6865 | likely_pathogenic | 0.7154 | pathogenic | -2.299 | Highly Destabilizing | 0.999 | D | 0.569 | neutral | N | 0.500428179 | None | None | N |
| R/I | 0.9804 | likely_pathogenic | 0.9799 | pathogenic | -1.249 | Destabilizing | 0.998 | D | 0.804 | deleterious | None | None | None | None | N |
| R/K | 0.3764 | ambiguous | 0.441 | ambiguous | -1.383 | Destabilizing | 0.709 | D | 0.482 | neutral | None | None | None | None | N |
| R/L | 0.9417 | likely_pathogenic | 0.9448 | pathogenic | -1.249 | Destabilizing | 0.996 | D | 0.679 | prob.neutral | N | 0.503933671 | None | None | N |
| R/M | 0.9405 | likely_pathogenic | 0.9444 | pathogenic | -1.641 | Destabilizing | 0.999 | D | 0.676 | prob.neutral | None | None | None | None | N |
| R/N | 0.9941 | likely_pathogenic | 0.9938 | pathogenic | -1.288 | Destabilizing | 0.994 | D | 0.548 | neutral | None | None | None | None | N |
| R/P | 0.9996 | likely_pathogenic | 0.9995 | pathogenic | -1.565 | Destabilizing | 1.0 | D | 0.763 | deleterious | D | 0.545764495 | None | None | N |
| R/Q | 0.5611 | ambiguous | 0.5563 | ambiguous | -1.254 | Destabilizing | 0.999 | D | 0.505 | neutral | None | None | None | None | N |
| R/S | 0.9938 | likely_pathogenic | 0.9934 | pathogenic | -2.307 | Highly Destabilizing | 0.99 | D | 0.597 | neutral | N | 0.476306309 | None | None | N |
| R/T | 0.989 | likely_pathogenic | 0.988 | pathogenic | -1.884 | Destabilizing | 0.997 | D | 0.655 | neutral | None | None | None | None | N |
| R/V | 0.9787 | likely_pathogenic | 0.9779 | pathogenic | -1.565 | Destabilizing | 0.991 | D | 0.782 | deleterious | None | None | None | None | N |
| R/W | 0.8705 | likely_pathogenic | 0.8852 | pathogenic | -0.945 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| R/Y | 0.9436 | likely_pathogenic | 0.9534 | pathogenic | -0.843 | Destabilizing | 0.998 | D | 0.775 | 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.