Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26289 | 79090;79091;79092 | chr2:178567267;178567266;178567265 | chr2:179431994;179431993;179431992 |
| N2AB | 24648 | 74167;74168;74169 | chr2:178567267;178567266;178567265 | chr2:179431994;179431993;179431992 |
| N2A | 23721 | 71386;71387;71388 | chr2:178567267;178567266;178567265 | chr2:179431994;179431993;179431992 |
| N2B | 17224 | 51895;51896;51897 | chr2:178567267;178567266;178567265 | chr2:179431994;179431993;179431992 |
| Novex-1 | 17349 | 52270;52271;52272 | chr2:178567267;178567266;178567265 | chr2:179431994;179431993;179431992 |
| Novex-2 | 17416 | 52471;52472;52473 | chr2:178567267;178567266;178567265 | chr2:179431994;179431993;179431992 |
| 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/R | None | None | 1.0 | D | 0.914 | 0.605 | 0.582512623681 | gnomAD-4.0.0 | 1.37568E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80423E-06 | 0 | 0 |
| P/S | rs1030641242  |
None | 1.0 | N | 0.874 | 0.53 | 0.465381546717 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/S | rs1030641242 |
None | 1.0 | N | 0.874 | 0.53 | 0.465381546717 | gnomAD-4.0.0 | 2.48957E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39892E-06 | 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 | 0.1512 | likely_benign | 0.1462 | benign | -1.638 | Destabilizing | 1.0 | D | 0.861 | deleterious | N | 0.509221813 | None | None | N |
| P/C | 0.694 | likely_pathogenic | 0.6416 | pathogenic | -1.033 | Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | N |
| P/D | 0.9314 | likely_pathogenic | 0.9092 | pathogenic | -1.758 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| P/E | 0.705 | likely_pathogenic | 0.6528 | pathogenic | -1.775 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| P/F | 0.7711 | likely_pathogenic | 0.7199 | pathogenic | -1.353 | Destabilizing | 1.0 | D | 0.914 | deleterious | None | None | None | None | N |
| P/G | 0.717 | likely_pathogenic | 0.6867 | pathogenic | -1.936 | Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| P/H | 0.5279 | ambiguous | 0.4854 | ambiguous | -1.467 | Destabilizing | 1.0 | D | 0.892 | deleterious | D | 0.529990871 | None | None | N |
| P/I | 0.4968 | ambiguous | 0.4252 | ambiguous | -0.912 | Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| P/K | 0.5251 | ambiguous | 0.4703 | ambiguous | -1.288 | Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| P/L | 0.2699 | likely_benign | 0.23 | benign | -0.912 | Destabilizing | 1.0 | D | 0.907 | deleterious | D | 0.523154016 | None | None | N |
| P/M | 0.5197 | ambiguous | 0.4557 | ambiguous | -0.652 | Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| P/N | 0.8146 | likely_pathogenic | 0.7764 | pathogenic | -1.052 | Destabilizing | 1.0 | D | 0.911 | deleterious | None | None | None | None | N |
| P/Q | 0.3794 | ambiguous | 0.3415 | ambiguous | -1.291 | Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| P/R | 0.4072 | ambiguous | 0.3561 | ambiguous | -0.718 | Destabilizing | 1.0 | D | 0.914 | deleterious | D | 0.528469934 | None | None | N |
| P/S | 0.3784 | ambiguous | 0.3557 | ambiguous | -1.52 | Destabilizing | 1.0 | D | 0.874 | deleterious | N | 0.50121142 | None | None | N |
| P/T | 0.3729 | ambiguous | 0.3279 | benign | -1.442 | Destabilizing | 1.0 | D | 0.866 | deleterious | N | 0.511290732 | None | None | N |
| P/V | 0.385 | ambiguous | 0.33 | benign | -1.122 | Destabilizing | 1.0 | D | 0.904 | deleterious | None | None | None | None | N |
| P/W | 0.9204 | likely_pathogenic | 0.8886 | pathogenic | -1.521 | Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| P/Y | 0.7992 | likely_pathogenic | 0.7596 | pathogenic | -1.256 | Destabilizing | 1.0 | D | 0.925 | 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.