Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27434 | 82525;82526;82527 | chr2:178563832;178563831;178563830 | chr2:179428559;179428558;179428557 |
| N2AB | 25793 | 77602;77603;77604 | chr2:178563832;178563831;178563830 | chr2:179428559;179428558;179428557 |
| N2A | 24866 | 74821;74822;74823 | chr2:178563832;178563831;178563830 | chr2:179428559;179428558;179428557 |
| N2B | 18369 | 55330;55331;55332 | chr2:178563832;178563831;178563830 | chr2:179428559;179428558;179428557 |
| Novex-1 | 18494 | 55705;55706;55707 | chr2:178563832;178563831;178563830 | chr2:179428559;179428558;179428557 |
| Novex-2 | 18561 | 55906;55907;55908 | chr2:178563832;178563831;178563830 | chr2:179428559;179428558;179428557 |
| 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 | rs777655678  |
-2.192 | 0.056 | D | 0.597 | 0.575 | 0.726614765145 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14811E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/F | rs777655678 |
-2.192 | 0.056 | D | 0.597 | 0.575 | 0.726614765145 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/F | rs777655678 |
-2.192 | 0.056 | D | 0.597 | 0.575 | 0.726614765145 | gnomAD-4.0.0 | 6.817E-06 | None | None | None | None | N | None | 1.33511E-05 | 0 | None | 0 | 0 | None | 0 | 1.6442E-04 | 6.7811E-06 | 1.09791E-05 | 0 |
| L/V | rs777655678 |
-2.04 | 0.805 | D | 0.773 | 0.656 | 0.72592812663 | 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 |
| L/V | rs777655678 |
-2.04 | 0.805 | D | 0.773 | 0.656 | 0.72592812663 | gnomAD-4.0.0 | 6.84228E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15934E-05 | 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 | 0.9892 | likely_pathogenic | 0.9848 | pathogenic | -2.905 | Highly Destabilizing | 0.916 | D | 0.8 | deleterious | None | None | None | None | N |
| L/C | 0.9795 | likely_pathogenic | 0.9691 | pathogenic | -2.27 | Highly Destabilizing | 0.999 | D | 0.796 | deleterious | None | None | None | None | N |
| L/D | 0.9997 | likely_pathogenic | 0.9995 | pathogenic | -3.462 | Highly Destabilizing | 0.996 | D | 0.876 | deleterious | None | None | None | None | N |
| L/E | 0.9987 | likely_pathogenic | 0.9978 | pathogenic | -3.224 | Highly Destabilizing | 0.996 | D | 0.866 | deleterious | None | None | None | None | N |
| L/F | 0.91 | likely_pathogenic | 0.8598 | pathogenic | -1.812 | Destabilizing | 0.056 | N | 0.597 | neutral | D | 0.65592182 | None | None | N |
| L/G | 0.9968 | likely_pathogenic | 0.996 | pathogenic | -3.466 | Highly Destabilizing | 0.987 | D | 0.871 | deleterious | None | None | None | None | N |
| L/H | 0.9951 | likely_pathogenic | 0.9921 | pathogenic | -2.933 | Highly Destabilizing | 0.999 | D | 0.859 | deleterious | D | 0.672980563 | None | None | N |
| L/I | 0.4705 | ambiguous | 0.386 | ambiguous | -1.263 | Destabilizing | 0.805 | D | 0.77 | deleterious | D | 0.620088101 | None | None | N |
| L/K | 0.9962 | likely_pathogenic | 0.9949 | pathogenic | -2.384 | Highly Destabilizing | 0.987 | D | 0.842 | deleterious | None | None | None | None | N |
| L/M | 0.6058 | likely_pathogenic | 0.5323 | ambiguous | -1.219 | Destabilizing | 0.693 | D | 0.713 | prob.delet. | None | None | None | None | N |
| L/N | 0.9968 | likely_pathogenic | 0.9949 | pathogenic | -2.797 | Highly Destabilizing | 0.996 | D | 0.879 | deleterious | None | None | None | None | N |
| L/P | 0.9969 | likely_pathogenic | 0.9957 | pathogenic | -1.794 | Destabilizing | 0.994 | D | 0.878 | deleterious | D | 0.672980563 | None | None | N |
| L/Q | 0.9945 | likely_pathogenic | 0.9903 | pathogenic | -2.646 | Highly Destabilizing | 0.987 | D | 0.855 | deleterious | None | None | None | None | N |
| L/R | 0.9915 | likely_pathogenic | 0.988 | pathogenic | -2.028 | Highly Destabilizing | 0.983 | D | 0.848 | deleterious | D | 0.647442451 | None | None | N |
| L/S | 0.9983 | likely_pathogenic | 0.9973 | pathogenic | -3.471 | Highly Destabilizing | 0.987 | D | 0.838 | deleterious | None | None | None | None | N |
| L/T | 0.9904 | likely_pathogenic | 0.9844 | pathogenic | -3.087 | Highly Destabilizing | 0.987 | D | 0.812 | deleterious | None | None | None | None | N |
| L/V | 0.6608 | likely_pathogenic | 0.5683 | pathogenic | -1.794 | Destabilizing | 0.805 | D | 0.773 | deleterious | D | 0.589320926 | None | None | N |
| L/W | 0.9896 | likely_pathogenic | 0.984 | pathogenic | -2.262 | Highly Destabilizing | 0.999 | D | 0.827 | deleterious | None | None | None | None | N |
| L/Y | 0.9878 | likely_pathogenic | 0.9809 | pathogenic | -2.011 | Highly Destabilizing | 0.95 | D | 0.819 | 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.