Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25788 | 77587;77588;77589 | chr2:178568770;178568769;178568768 | chr2:179433497;179433496;179433495 |
| N2AB | 24147 | 72664;72665;72666 | chr2:178568770;178568769;178568768 | chr2:179433497;179433496;179433495 |
| N2A | 23220 | 69883;69884;69885 | chr2:178568770;178568769;178568768 | chr2:179433497;179433496;179433495 |
| N2B | 16723 | 50392;50393;50394 | chr2:178568770;178568769;178568768 | chr2:179433497;179433496;179433495 |
| Novex-1 | 16848 | 50767;50768;50769 | chr2:178568770;178568769;178568768 | chr2:179433497;179433496;179433495 |
| Novex-2 | 16915 | 50968;50969;50970 | chr2:178568770;178568769;178568768 | chr2:179433497;179433496;179433495 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | None | None | 0.949 | N | 0.557 | 0.226 | 0.267755039894 | gnomAD-4.0.0 | 2.40065E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.62501E-06 | 0 | 0 |
| P/S | rs939575680  |
None | 0.832 | N | 0.341 | 0.279 | 0.258283824007 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 1.10132E-03 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs939575680 |
None | 0.832 | N | 0.341 | 0.279 | 0.258283824007 | gnomAD-4.0.0 | 6.57756E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.175 | likely_benign | 0.15 | benign | -0.854 | Destabilizing | 0.949 | D | 0.557 | neutral | N | 0.465169677 | None | None | N |
| P/C | 0.831 | likely_pathogenic | 0.7809 | pathogenic | -0.743 | Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | N |
| P/D | 0.849 | likely_pathogenic | 0.8075 | pathogenic | -0.64 | Destabilizing | 0.977 | D | 0.696 | prob.delet. | None | None | None | None | N |
| P/E | 0.7451 | likely_pathogenic | 0.6855 | pathogenic | -0.667 | Destabilizing | 0.985 | D | 0.706 | prob.delet. | None | None | None | None | N |
| P/F | 0.909 | likely_pathogenic | 0.8573 | pathogenic | -0.635 | Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | N |
| P/G | 0.5687 | likely_pathogenic | 0.51 | ambiguous | -1.103 | Destabilizing | 0.992 | D | 0.665 | prob.neutral | None | None | None | None | N |
| P/H | 0.5811 | likely_pathogenic | 0.5108 | ambiguous | -0.526 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| P/I | 0.8513 | likely_pathogenic | 0.7777 | pathogenic | -0.3 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| P/K | 0.7861 | likely_pathogenic | 0.7337 | pathogenic | -0.828 | Destabilizing | 1.0 | D | 0.703 | prob.delet. | None | None | None | None | N |
| P/L | 0.4909 | ambiguous | 0.3964 | ambiguous | -0.3 | Destabilizing | 1.0 | D | 0.699 | prob.delet. | N | 0.477259998 | None | None | N |
| P/M | 0.7935 | likely_pathogenic | 0.7092 | pathogenic | -0.418 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| P/N | 0.6725 | likely_pathogenic | 0.5984 | pathogenic | -0.687 | Destabilizing | 0.996 | D | 0.799 | deleterious | None | None | None | None | N |
| P/Q | 0.5113 | ambiguous | 0.4458 | ambiguous | -0.835 | Destabilizing | 0.999 | D | 0.775 | deleterious | N | 0.498152638 | None | None | N |
| P/R | 0.6221 | likely_pathogenic | 0.5625 | ambiguous | -0.324 | Destabilizing | 1.0 | D | 0.827 | deleterious | N | 0.516256893 | None | None | N |
| P/S | 0.2626 | likely_benign | 0.2268 | benign | -1.122 | Destabilizing | 0.832 | D | 0.341 | neutral | N | 0.472046212 | None | None | N |
| P/T | 0.3485 | ambiguous | 0.279 | benign | -1.038 | Destabilizing | 0.966 | D | 0.666 | prob.neutral | N | 0.475996232 | None | None | N |
| P/V | 0.6796 | likely_pathogenic | 0.5737 | pathogenic | -0.449 | Destabilizing | 0.999 | D | 0.787 | deleterious | None | None | None | None | N |
| P/W | 0.948 | likely_pathogenic | 0.9169 | pathogenic | -0.795 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| P/Y | 0.8798 | likely_pathogenic | 0.8296 | pathogenic | -0.494 | Destabilizing | 1.0 | D | 0.869 | 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.