Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2929 | 9010;9011;9012 | chr2:178769796;178769795;178769794 | chr2:179634523;179634522;179634521 |
| N2AB | 2929 | 9010;9011;9012 | chr2:178769796;178769795;178769794 | chr2:179634523;179634522;179634521 |
| N2A | 2929 | 9010;9011;9012 | chr2:178769796;178769795;178769794 | chr2:179634523;179634522;179634521 |
| N2B | 2883 | 8872;8873;8874 | chr2:178769796;178769795;178769794 | chr2:179634523;179634522;179634521 |
| Novex-1 | 2883 | 8872;8873;8874 | chr2:178769796;178769795;178769794 | chr2:179634523;179634522;179634521 |
| Novex-2 | 2883 | 8872;8873;8874 | chr2:178769796;178769795;178769794 | chr2:179634523;179634522;179634521 |
| Novex-3 | 2929 | 9010;9011;9012 | chr2:178769796;178769795;178769794 | chr2:179634523;179634522;179634521 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | None | None | 1.0 | N | 0.737 | 0.428 | 0.467329424371 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/R | rs757111808  |
-1.237 | 1.0 | D | 0.811 | 0.762 | 0.898047849171 | gnomAD-2.1.1 | 1.2E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.65E-05 | 0 |
| I/R | rs757111808 |
-1.237 | 1.0 | D | 0.811 | 0.762 | 0.898047849171 | gnomAD-4.0.0 | 1.11334E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.71392E-05 | 1.43271E-05 | 0 |
| I/T | rs757111808 |
-2.331 | 1.0 | D | 0.721 | 0.713 | 0.777605954234 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 2.89E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs757111808 |
-2.331 | 1.0 | D | 0.721 | 0.713 | 0.777605954234 | gnomAD-4.0.0 | 1.59049E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85654E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9313 | likely_pathogenic | 0.9352 | pathogenic | -2.058 | Highly Destabilizing | 0.999 | D | 0.533 | neutral | None | None | None | None | N |
| I/C | 0.9873 | likely_pathogenic | 0.9856 | pathogenic | -1.132 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| I/D | 0.9948 | likely_pathogenic | 0.9948 | pathogenic | -1.951 | Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| I/E | 0.9833 | likely_pathogenic | 0.9833 | pathogenic | -1.833 | Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| I/F | 0.6819 | likely_pathogenic | 0.6184 | pathogenic | -1.286 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| I/G | 0.9902 | likely_pathogenic | 0.9899 | pathogenic | -2.48 | Highly Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | N |
| I/H | 0.9832 | likely_pathogenic | 0.9824 | pathogenic | -1.672 | Destabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | N |
| I/K | 0.9612 | likely_pathogenic | 0.962 | pathogenic | -1.556 | Destabilizing | 1.0 | D | 0.799 | deleterious | D | 0.622544883 | None | None | N |
| I/L | 0.5137 | ambiguous | 0.477 | ambiguous | -0.901 | Destabilizing | 0.993 | D | 0.351 | neutral | N | 0.512318323 | None | None | N |
| I/M | 0.2959 | likely_benign | 0.2806 | benign | -0.675 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.515251275 | None | None | N |
| I/N | 0.9521 | likely_pathogenic | 0.9493 | pathogenic | -1.595 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| I/P | 0.9909 | likely_pathogenic | 0.9904 | pathogenic | -1.262 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| I/Q | 0.9759 | likely_pathogenic | 0.9759 | pathogenic | -1.634 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| I/R | 0.9438 | likely_pathogenic | 0.9412 | pathogenic | -1.061 | Destabilizing | 1.0 | D | 0.811 | deleterious | D | 0.647043704 | None | None | N |
| I/S | 0.954 | likely_pathogenic | 0.9541 | pathogenic | -2.207 | Highly Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | N |
| I/T | 0.843 | likely_pathogenic | 0.8578 | pathogenic | -1.961 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | D | 0.54815626 | None | None | N |
| I/V | 0.3315 | likely_benign | 0.3116 | benign | -1.262 | Destabilizing | 0.993 | D | 0.344 | neutral | N | 0.504082517 | None | None | N |
| I/W | 0.9742 | likely_pathogenic | 0.9739 | pathogenic | -1.513 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| I/Y | 0.9318 | likely_pathogenic | 0.9115 | pathogenic | -1.243 | Destabilizing | 1.0 | D | 0.783 | 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.