Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21248 | 63967;63968;63969 | chr2:178587567;178587566;178587565 | chr2:179452294;179452293;179452292 |
| N2AB | 19607 | 59044;59045;59046 | chr2:178587567;178587566;178587565 | chr2:179452294;179452293;179452292 |
| N2A | 18680 | 56263;56264;56265 | chr2:178587567;178587566;178587565 | chr2:179452294;179452293;179452292 |
| N2B | 12183 | 36772;36773;36774 | chr2:178587567;178587566;178587565 | chr2:179452294;179452293;179452292 |
| Novex-1 | 12308 | 37147;37148;37149 | chr2:178587567;178587566;178587565 | chr2:179452294;179452293;179452292 |
| Novex-2 | 12375 | 37348;37349;37350 | chr2:178587567;178587566;178587565 | chr2:179452294;179452293;179452292 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs771468174  |
-1.592 | 0.978 | D | 0.833 | 0.453 | 0.732364685296 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.69E-05 | 0 | 0 |
| L/F | rs771468174 |
-1.592 | 0.978 | D | 0.833 | 0.453 | 0.732364685296 | gnomAD-4.0.0 | 6.16354E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87913E-05 | 0 | 6.29937E-06 | 0 | 1.65881E-05 |
| L/P | rs745323281 |
-1.839 | 0.996 | N | 0.867 | 0.657 | 0.85706450173 | gnomAD-2.1.1 | 3.24E-05 | None | None | None | None | N | None | 0 | 8.54E-05 | None | 0 | 0 | None | 0 | None | 0 | 4.72E-05 | 0 |
| L/P | rs745323281 |
-1.839 | 0.996 | N | 0.867 | 0.657 | 0.85706450173 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| L/P | rs745323281 |
-1.839 | 0.996 | N | 0.867 | 0.657 | 0.85706450173 | gnomAD-4.0.0 | 2.10913E-05 | None | None | None | None | N | None | 0 | 5.01387E-05 | None | 0 | 0 | None | 0 | 0 | 2.62908E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.3289 | likely_benign | 0.3452 | ambiguous | -2.237 | Highly Destabilizing | 0.895 | D | 0.659 | neutral | None | None | None | None | N |
| L/C | 0.6881 | likely_pathogenic | 0.7053 | pathogenic | -1.603 | Destabilizing | 0.999 | D | 0.841 | deleterious | None | None | None | None | N |
| L/D | 0.9979 | likely_pathogenic | 0.9985 | pathogenic | -2.16 | Highly Destabilizing | 0.997 | D | 0.873 | deleterious | None | None | None | None | N |
| L/E | 0.9889 | likely_pathogenic | 0.9914 | pathogenic | -2.069 | Highly Destabilizing | 0.992 | D | 0.863 | deleterious | None | None | None | None | N |
| L/F | 0.8468 | likely_pathogenic | 0.8558 | pathogenic | -1.455 | Destabilizing | 0.978 | D | 0.833 | deleterious | D | 0.526865271 | None | None | N |
| L/G | 0.9062 | likely_pathogenic | 0.9087 | pathogenic | -2.664 | Highly Destabilizing | 0.992 | D | 0.868 | deleterious | None | None | None | None | N |
| L/H | 0.9865 | likely_pathogenic | 0.9885 | pathogenic | -1.968 | Destabilizing | 0.999 | D | 0.855 | deleterious | D | 0.52737225 | None | None | N |
| L/I | 0.1083 | likely_benign | 0.1383 | benign | -1.072 | Destabilizing | 0.688 | D | 0.6 | neutral | N | 0.502984566 | None | None | N |
| L/K | 0.9916 | likely_pathogenic | 0.9928 | pathogenic | -1.694 | Destabilizing | 0.992 | D | 0.856 | deleterious | None | None | None | None | N |
| L/M | 0.2655 | likely_benign | 0.2791 | benign | -0.951 | Destabilizing | 0.983 | D | 0.798 | deleterious | None | None | None | None | N |
| L/N | 0.9848 | likely_pathogenic | 0.9891 | pathogenic | -1.682 | Destabilizing | 0.997 | D | 0.866 | deleterious | None | None | None | None | N |
| L/P | 0.9902 | likely_pathogenic | 0.9934 | pathogenic | -1.434 | Destabilizing | 0.996 | D | 0.867 | deleterious | N | 0.509014505 | None | None | N |
| L/Q | 0.9625 | likely_pathogenic | 0.9671 | pathogenic | -1.765 | Destabilizing | 0.997 | D | 0.862 | deleterious | None | None | None | None | N |
| L/R | 0.9792 | likely_pathogenic | 0.9812 | pathogenic | -1.174 | Destabilizing | 0.989 | D | 0.864 | deleterious | D | 0.52711876 | None | None | N |
| L/S | 0.8669 | likely_pathogenic | 0.8908 | pathogenic | -2.35 | Highly Destabilizing | 0.983 | D | 0.849 | deleterious | None | None | None | None | N |
| L/T | 0.5889 | likely_pathogenic | 0.6536 | pathogenic | -2.134 | Highly Destabilizing | 0.983 | D | 0.802 | deleterious | None | None | None | None | N |
| L/V | 0.0671 | likely_benign | 0.0996 | benign | -1.434 | Destabilizing | 0.039 | N | 0.375 | neutral | N | 0.440757098 | None | None | N |
| L/W | 0.9869 | likely_pathogenic | 0.9889 | pathogenic | -1.666 | Destabilizing | 0.999 | D | 0.822 | deleterious | None | None | None | None | N |
| L/Y | 0.9829 | likely_pathogenic | 0.9859 | pathogenic | -1.43 | Destabilizing | 0.992 | D | 0.845 | 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.