Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29574 | 88945;88946;88947 | chr2:178554627;178554626;178554625 | chr2:179419354;179419353;179419352 |
| N2AB | 27933 | 84022;84023;84024 | chr2:178554627;178554626;178554625 | chr2:179419354;179419353;179419352 |
| N2A | 27006 | 81241;81242;81243 | chr2:178554627;178554626;178554625 | chr2:179419354;179419353;179419352 |
| N2B | 20509 | 61750;61751;61752 | chr2:178554627;178554626;178554625 | chr2:179419354;179419353;179419352 |
| Novex-1 | 20634 | 62125;62126;62127 | chr2:178554627;178554626;178554625 | chr2:179419354;179419353;179419352 |
| Novex-2 | 20701 | 62326;62327;62328 | chr2:178554627;178554626;178554625 | chr2:179419354;179419353;179419352 |
| 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 | rs200513274  |
-1.687 | 1.0 | N | 0.885 | 0.374 | None | gnomAD-2.1.1 | 2.60645E-04 | None | None | None | None | N | None | 1.23957E-04 | 2.83E-05 | None | 0 | 4.10298E-04 | None | 2.61455E-04 | None | 0 | 3.98624E-04 | 2.80899E-04 |
| R/C | rs200513274 |
-1.687 | 1.0 | N | 0.885 | 0.374 | None | gnomAD-3.1.2 | 2.89283E-04 | None | None | None | None | N | None | 1.20691E-04 | 0 | 0 | 0 | 7.72201E-04 | None | 0 | 0 | 5.14555E-04 | 0 | 0 |
| R/C | rs200513274 |
-1.687 | 1.0 | N | 0.885 | 0.374 | None | 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 | rs200513274 |
-1.687 | 1.0 | N | 0.885 | 0.374 | None | gnomAD-4.0.0 | 4.75884E-04 | None | None | None | None | N | None | 1.06627E-04 | 0 | None | 0 | 3.79007E-04 | None | 1.56265E-05 | 0 | 5.8059E-04 | 3.51363E-04 | 4.00128E-04 |
| R/G | rs200513274 |
-2.568 | 1.0 | N | 0.783 | 0.466 | 0.614107689767 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/G | rs200513274 |
-2.568 | 1.0 | N | 0.783 | 0.466 | 0.614107689767 | gnomAD-4.0.0 | 2.05251E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79885E-06 | 1.15937E-05 | 0 |
| R/H | rs111727915 |
-2.472 | 1.0 | N | 0.787 | 0.404 | None | gnomAD-2.1.1 | 5.3912E-04 | None | None | None | None | N | None | 2.06629E-03 | 9.89819E-04 | None | 1.74149E-03 | 0 | None | 3.27E-05 | None | 4E-05 | 3.12627E-04 | 8.4246E-04 |
| R/H | rs111727915 |
-2.472 | 1.0 | N | 0.787 | 0.404 | None | gnomAD-3.1.2 | 8.74057E-04 | None | None | None | None | N | None | 2.05096E-03 | 1.30959E-03 | 0 | 1.72911E-03 | 0 | None | 0 | 0 | 3.0866E-04 | 0 | 4.78469E-04 |
| R/H | rs111727915 |
-2.472 | 1.0 | N | 0.787 | 0.404 | None | 1000 genomes | 9.98403E-04 | None | None | None | None | N | None | 1.5E-03 | 2.9E-03 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| R/H | rs111727915 |
-2.472 | 1.0 | N | 0.787 | 0.404 | None | gnomAD-4.0.0 | 3.14762E-04 | None | None | None | None | N | None | 1.9855E-03 | 9.83071E-04 | None | 1.58773E-03 | 0 | None | 1.56226E-05 | 1.32013E-03 | 1.70361E-04 | 6.58733E-05 | 5.9219E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.98 | likely_pathogenic | 0.9823 | pathogenic | -2.153 | Highly Destabilizing | 0.999 | D | 0.561 | neutral | None | None | None | None | N |
| R/C | 0.6076 | likely_pathogenic | 0.6211 | pathogenic | -1.928 | Destabilizing | 1.0 | D | 0.885 | deleterious | N | 0.472030802 | None | None | N |
| R/D | 0.9984 | likely_pathogenic | 0.9985 | pathogenic | -0.845 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| R/E | 0.974 | likely_pathogenic | 0.9746 | pathogenic | -0.633 | Destabilizing | 0.999 | D | 0.581 | neutral | None | None | None | None | N |
| R/F | 0.993 | likely_pathogenic | 0.9934 | pathogenic | -1.386 | Destabilizing | 1.0 | D | 0.892 | deleterious | None | None | None | None | N |
| R/G | 0.9637 | likely_pathogenic | 0.9673 | pathogenic | -2.485 | Highly Destabilizing | 1.0 | D | 0.783 | deleterious | N | 0.488071142 | None | None | N |
| R/H | 0.7671 | likely_pathogenic | 0.7586 | pathogenic | -2.25 | Highly Destabilizing | 1.0 | D | 0.787 | deleterious | N | 0.496971912 | None | None | N |
| R/I | 0.9817 | likely_pathogenic | 0.9822 | pathogenic | -1.186 | Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| R/K | 0.448 | ambiguous | 0.4362 | ambiguous | -1.304 | Destabilizing | 0.998 | D | 0.483 | neutral | None | None | None | None | N |
| R/L | 0.947 | likely_pathogenic | 0.9538 | pathogenic | -1.186 | Destabilizing | 1.0 | D | 0.783 | deleterious | N | 0.489121099 | None | None | N |
| R/M | 0.936 | likely_pathogenic | 0.9397 | pathogenic | -1.659 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| R/N | 0.994 | likely_pathogenic | 0.9939 | pathogenic | -1.205 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| R/P | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -1.499 | Destabilizing | 1.0 | D | 0.883 | deleterious | N | 0.514822678 | None | None | N |
| R/Q | 0.4785 | ambiguous | 0.4711 | ambiguous | -1.138 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| R/S | 0.9932 | likely_pathogenic | 0.9935 | pathogenic | -2.187 | Highly Destabilizing | 1.0 | D | 0.795 | deleterious | N | 0.51222762 | None | None | N |
| R/T | 0.9837 | likely_pathogenic | 0.9837 | pathogenic | -1.767 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| R/V | 0.9776 | likely_pathogenic | 0.9784 | pathogenic | -1.499 | Destabilizing | 1.0 | D | 0.88 | deleterious | None | None | None | None | N |
| R/W | 0.9171 | likely_pathogenic | 0.9242 | pathogenic | -0.837 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| R/Y | 0.9715 | likely_pathogenic | 0.9734 | pathogenic | -0.732 | Destabilizing | 1.0 | D | 0.909 | 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.