Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23721 | 71386;71387;71388 | chr2:178574971;178574970;178574969 | chr2:179439698;179439697;179439696 |
| N2AB | 22080 | 66463;66464;66465 | chr2:178574971;178574970;178574969 | chr2:179439698;179439697;179439696 |
| N2A | 21153 | 63682;63683;63684 | chr2:178574971;178574970;178574969 | chr2:179439698;179439697;179439696 |
| N2B | 14656 | 44191;44192;44193 | chr2:178574971;178574970;178574969 | chr2:179439698;179439697;179439696 |
| Novex-1 | 14781 | 44566;44567;44568 | chr2:178574971;178574970;178574969 | chr2:179439698;179439697;179439696 |
| Novex-2 | 14848 | 44767;44768;44769 | chr2:178574971;178574970;178574969 | chr2:179439698;179439697;179439696 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/F | None | None | 0.317 | N | 0.669 | 0.189 | 0.451786746415 | gnomAD-4.0.0 | 1.59248E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85974E-06 | 0 | 0 |
| I/V | rs773072591  |
-1.24 | None | N | 0.249 | 0.057 | 0.19670166235 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.25327E-04 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs773072591 |
-1.24 | None | N | 0.249 | 0.057 | 0.19670166235 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93949E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs773072591 |
-1.24 | None | N | 0.249 | 0.057 | 0.19670166235 | gnomAD-4.0.0 | 8.97243E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.70574E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9517 | likely_pathogenic | 0.946 | pathogenic | -2.754 | Highly Destabilizing | 0.035 | N | 0.574 | neutral | None | None | None | None | N |
| I/C | 0.9442 | likely_pathogenic | 0.9428 | pathogenic | -2.201 | Highly Destabilizing | 0.824 | D | 0.761 | deleterious | None | None | None | None | N |
| I/D | 0.9992 | likely_pathogenic | 0.999 | pathogenic | -3.111 | Highly Destabilizing | 0.555 | D | 0.807 | deleterious | None | None | None | None | N |
| I/E | 0.9973 | likely_pathogenic | 0.9967 | pathogenic | -2.867 | Highly Destabilizing | 0.555 | D | 0.8 | deleterious | None | None | None | None | N |
| I/F | 0.4882 | ambiguous | 0.4669 | ambiguous | -1.687 | Destabilizing | 0.317 | N | 0.669 | neutral | N | 0.466024916 | None | None | N |
| I/G | 0.9925 | likely_pathogenic | 0.991 | pathogenic | -3.332 | Highly Destabilizing | 0.262 | N | 0.785 | deleterious | None | None | None | None | N |
| I/H | 0.9949 | likely_pathogenic | 0.9936 | pathogenic | -2.752 | Highly Destabilizing | 0.935 | D | 0.813 | deleterious | None | None | None | None | N |
| I/K | 0.9952 | likely_pathogenic | 0.9938 | pathogenic | -2.238 | Highly Destabilizing | 0.555 | D | 0.803 | deleterious | None | None | None | None | N |
| I/L | 0.2082 | likely_benign | 0.2107 | benign | -1.072 | Destabilizing | 0.005 | N | 0.38 | neutral | N | 0.378978975 | None | None | N |
| I/M | 0.3405 | ambiguous | 0.3457 | ambiguous | -1.088 | Destabilizing | 0.317 | N | 0.644 | neutral | N | 0.500135396 | None | None | N |
| I/N | 0.9892 | likely_pathogenic | 0.9875 | pathogenic | -2.649 | Highly Destabilizing | 0.741 | D | 0.823 | deleterious | N | 0.467292363 | None | None | N |
| I/P | 0.9944 | likely_pathogenic | 0.9913 | pathogenic | -1.615 | Destabilizing | 0.791 | D | 0.813 | deleterious | None | None | None | None | N |
| I/Q | 0.9952 | likely_pathogenic | 0.994 | pathogenic | -2.485 | Highly Destabilizing | 0.791 | D | 0.827 | deleterious | None | None | None | None | N |
| I/R | 0.9922 | likely_pathogenic | 0.9893 | pathogenic | -1.935 | Destabilizing | 0.555 | D | 0.824 | deleterious | None | None | None | None | N |
| I/S | 0.9811 | likely_pathogenic | 0.9798 | pathogenic | -3.375 | Highly Destabilizing | 0.117 | N | 0.761 | deleterious | N | 0.467038874 | None | None | N |
| I/T | 0.9524 | likely_pathogenic | 0.9528 | pathogenic | -2.972 | Highly Destabilizing | 0.062 | N | 0.667 | neutral | N | 0.467038874 | None | None | N |
| I/V | 0.0815 | likely_benign | 0.0764 | benign | -1.615 | Destabilizing | None | N | 0.249 | neutral | N | 0.352654458 | None | None | N |
| I/W | 0.9901 | likely_pathogenic | 0.9869 | pathogenic | -2.074 | Highly Destabilizing | 0.935 | D | 0.811 | deleterious | None | None | None | None | N |
| I/Y | 0.9558 | likely_pathogenic | 0.947 | pathogenic | -1.798 | Destabilizing | 0.555 | D | 0.773 | 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.