Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26115 | 78568;78569;78570 | chr2:178567789;178567788;178567787 | chr2:179432516;179432515;179432514 |
| N2AB | 24474 | 73645;73646;73647 | chr2:178567789;178567788;178567787 | chr2:179432516;179432515;179432514 |
| N2A | 23547 | 70864;70865;70866 | chr2:178567789;178567788;178567787 | chr2:179432516;179432515;179432514 |
| N2B | 17050 | 51373;51374;51375 | chr2:178567789;178567788;178567787 | chr2:179432516;179432515;179432514 |
| Novex-1 | 17175 | 51748;51749;51750 | chr2:178567789;178567788;178567787 | chr2:179432516;179432515;179432514 |
| Novex-2 | 17242 | 51949;51950;51951 | chr2:178567789;178567788;178567787 | chr2:179432516;179432515;179432514 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | rs772167133  |
-0.181 | 0.999 | N | 0.688 | 0.581 | 0.447901950027 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 0 | 0 |
| D/A | rs772167133 |
-0.181 | 0.999 | N | 0.688 | 0.581 | 0.447901950027 | gnomAD-4.0.0 | 1.2318E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.97133E-04 | 1.65706E-05 |
| D/N | rs377493254 |
-0.269 | 0.884 | N | 0.251 | 0.328 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.9027 | likely_pathogenic | 0.8358 | pathogenic | -0.602 | Destabilizing | 0.999 | D | 0.688 | prob.neutral | N | 0.497501663 | None | None | I |
| D/C | 0.9833 | likely_pathogenic | 0.964 | pathogenic | -0.224 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| D/E | 0.9142 | likely_pathogenic | 0.8006 | pathogenic | -0.767 | Destabilizing | 0.996 | D | 0.442 | neutral | N | 0.501260645 | None | None | I |
| D/F | 0.9911 | likely_pathogenic | 0.9825 | pathogenic | -0.625 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | I |
| D/G | 0.8706 | likely_pathogenic | 0.8284 | pathogenic | -0.915 | Destabilizing | 0.996 | D | 0.637 | neutral | D | 0.527331072 | None | None | I |
| D/H | 0.945 | likely_pathogenic | 0.9075 | pathogenic | -1.056 | Destabilizing | 1.0 | D | 0.765 | deleterious | N | 0.516860139 | None | None | I |
| D/I | 0.9809 | likely_pathogenic | 0.9531 | pathogenic | 0.215 | Stabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| D/K | 0.9824 | likely_pathogenic | 0.9696 | pathogenic | -0.486 | Destabilizing | 0.999 | D | 0.686 | prob.neutral | None | None | None | None | I |
| D/L | 0.9737 | likely_pathogenic | 0.951 | pathogenic | 0.215 | Stabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | I |
| D/M | 0.9907 | likely_pathogenic | 0.9795 | pathogenic | 0.763 | Stabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | I |
| D/N | 0.2239 | likely_benign | 0.2172 | benign | -0.784 | Destabilizing | 0.884 | D | 0.251 | neutral | N | 0.479980066 | None | None | I |
| D/P | 0.9848 | likely_pathogenic | 0.979 | pathogenic | -0.033 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| D/Q | 0.9739 | likely_pathogenic | 0.9444 | pathogenic | -0.668 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | I |
| D/R | 0.9808 | likely_pathogenic | 0.9658 | pathogenic | -0.492 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | I |
| D/S | 0.5641 | likely_pathogenic | 0.4843 | ambiguous | -1.037 | Destabilizing | 0.997 | D | 0.61 | neutral | None | None | None | None | I |
| D/T | 0.7408 | likely_pathogenic | 0.6406 | pathogenic | -0.78 | Destabilizing | 0.999 | D | 0.687 | prob.neutral | None | None | None | None | I |
| D/V | 0.9434 | likely_pathogenic | 0.8816 | pathogenic | -0.033 | Destabilizing | 1.0 | D | 0.757 | deleterious | D | 0.526063624 | None | None | I |
| D/W | 0.9981 | likely_pathogenic | 0.9964 | pathogenic | -0.579 | Destabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | I |
| D/Y | 0.9346 | likely_pathogenic | 0.888 | pathogenic | -0.429 | Destabilizing | 1.0 | D | 0.756 | deleterious | D | 0.553829118 | None | None | I |
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.