Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18516 | 55771;55772;55773 | chr2:178601451;178601450;178601449 | chr2:179466178;179466177;179466176 |
| N2AB | 16875 | 50848;50849;50850 | chr2:178601451;178601450;178601449 | chr2:179466178;179466177;179466176 |
| N2A | 15948 | 48067;48068;48069 | chr2:178601451;178601450;178601449 | chr2:179466178;179466177;179466176 |
| N2B | 9451 | 28576;28577;28578 | chr2:178601451;178601450;178601449 | chr2:179466178;179466177;179466176 |
| Novex-1 | 9576 | 28951;28952;28953 | chr2:178601451;178601450;178601449 | chr2:179466178;179466177;179466176 |
| Novex-2 | 9643 | 29152;29153;29154 | chr2:178601451;178601450;178601449 | chr2:179466178;179466177;179466176 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs146608896  |
-3.45 | 0.939 | N | 0.659 | 0.505 | None | gnomAD-2.1.1 | 7.00686E-04 | None | None | None | None | N | None | 7.81702E-03 | 1.70049E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.40607E-04 |
| I/T | rs146608896 |
-3.45 | 0.939 | N | 0.659 | 0.505 | None | gnomAD-3.1.2 | 2.45446E-03 | None | None | None | None | N | None | 8.25967E-03 | 1.77212E-03 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.91205E-03 |
| I/T | rs146608896 |
-3.45 | 0.939 | N | 0.659 | 0.505 | None | 1000 genomes | 2.79553E-03 | None | None | None | None | N | None | 9.1E-03 | 1.4E-03 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| I/T | rs146608896 |
-3.45 | 0.939 | N | 0.659 | 0.505 | None | gnomAD-4.0.0 | 4.2468E-04 | None | None | None | None | N | None | 7.96425E-03 | 7.67665E-04 | None | 0 | 0 | None | 0 | 1.6518E-04 | 4.23959E-06 | 0 | 5.76443E-04 |
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 | 0.9049 | likely_pathogenic | 0.9326 | pathogenic | -3.294 | Highly Destabilizing | 0.91 | D | 0.671 | neutral | None | None | None | None | N |
| I/C | 0.972 | likely_pathogenic | 0.9788 | pathogenic | -2.51 | Highly Destabilizing | 0.999 | D | 0.768 | deleterious | None | None | None | None | N |
| I/D | 0.9996 | likely_pathogenic | 0.9997 | pathogenic | -3.851 | Highly Destabilizing | 0.998 | D | 0.899 | deleterious | None | None | None | None | N |
| I/E | 0.998 | likely_pathogenic | 0.9986 | pathogenic | -3.538 | Highly Destabilizing | 0.993 | D | 0.893 | deleterious | None | None | None | None | N |
| I/F | 0.8715 | likely_pathogenic | 0.9199 | pathogenic | -1.857 | Destabilizing | 0.991 | D | 0.665 | neutral | D | 0.531519171 | None | None | N |
| I/G | 0.9946 | likely_pathogenic | 0.9969 | pathogenic | -3.873 | Highly Destabilizing | 0.993 | D | 0.888 | deleterious | None | None | None | None | N |
| I/H | 0.9987 | likely_pathogenic | 0.9991 | pathogenic | -3.355 | Highly Destabilizing | 0.999 | D | 0.885 | deleterious | None | None | None | None | N |
| I/K | 0.9962 | likely_pathogenic | 0.9973 | pathogenic | -2.593 | Highly Destabilizing | 0.993 | D | 0.895 | deleterious | None | None | None | None | N |
| I/L | 0.3389 | likely_benign | 0.4158 | ambiguous | -1.528 | Destabilizing | 0.58 | D | 0.348 | neutral | N | 0.496570308 | None | None | N |
| I/M | 0.4781 | ambiguous | 0.5792 | pathogenic | -1.774 | Destabilizing | 0.991 | D | 0.653 | neutral | N | 0.483700866 | None | None | N |
| I/N | 0.9953 | likely_pathogenic | 0.9962 | pathogenic | -3.271 | Highly Destabilizing | 0.997 | D | 0.908 | deleterious | D | 0.53177266 | None | None | N |
| I/P | 0.994 | likely_pathogenic | 0.9956 | pathogenic | -2.112 | Highly Destabilizing | 0.998 | D | 0.902 | deleterious | None | None | None | None | N |
| I/Q | 0.9966 | likely_pathogenic | 0.9978 | pathogenic | -2.938 | Highly Destabilizing | 0.998 | D | 0.911 | deleterious | None | None | None | None | N |
| I/R | 0.9936 | likely_pathogenic | 0.9957 | pathogenic | -2.491 | Highly Destabilizing | 0.998 | D | 0.911 | deleterious | None | None | None | None | N |
| I/S | 0.9829 | likely_pathogenic | 0.9879 | pathogenic | -3.818 | Highly Destabilizing | 0.991 | D | 0.823 | deleterious | D | 0.53177266 | None | None | N |
| I/T | 0.8563 | likely_pathogenic | 0.8861 | pathogenic | -3.357 | Highly Destabilizing | 0.939 | D | 0.659 | neutral | N | 0.520162865 | None | None | N |
| I/V | 0.0998 | likely_benign | 0.113 | benign | -2.112 | Highly Destabilizing | 0.02 | N | 0.22 | neutral | N | 0.409076249 | None | None | N |
| I/W | 0.9977 | likely_pathogenic | 0.9986 | pathogenic | -2.222 | Highly Destabilizing | 0.999 | D | 0.854 | deleterious | None | None | None | None | N |
| I/Y | 0.9934 | likely_pathogenic | 0.9956 | pathogenic | -2.156 | Highly Destabilizing | 0.998 | D | 0.754 | 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.