Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26277 | 79054;79055;79056 | chr2:178567303;178567302;178567301 | chr2:179432030;179432029;179432028 |
| N2AB | 24636 | 74131;74132;74133 | chr2:178567303;178567302;178567301 | chr2:179432030;179432029;179432028 |
| N2A | 23709 | 71350;71351;71352 | chr2:178567303;178567302;178567301 | chr2:179432030;179432029;179432028 |
| N2B | 17212 | 51859;51860;51861 | chr2:178567303;178567302;178567301 | chr2:179432030;179432029;179432028 |
| Novex-1 | 17337 | 52234;52235;52236 | chr2:178567303;178567302;178567301 | chr2:179432030;179432029;179432028 |
| Novex-2 | 17404 | 52435;52436;52437 | chr2:178567303;178567302;178567301 | chr2:179432030;179432029;179432028 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs1265065751  |
-1.012 | 0.08 | N | 0.24 | 0.113 | 0.293147016451 | gnomAD-2.1.1 | 4.13E-06 | None | None | None | None | N | None | 0 | 3E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| F/L | rs1265065751 |
-1.012 | 0.08 | N | 0.24 | 0.113 | 0.293147016451 | gnomAD-4.0.0 | 1.60822E-06 | None | None | None | None | N | None | 0 | 2.35228E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| F/Y | None | None | 0.001 | N | 0.131 | 0.2 | 0.328486982098 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.4379 | ambiguous | 0.371 | ambiguous | -2.455 | Highly Destabilizing | 0.103 | N | 0.447 | neutral | None | None | None | None | N |
| F/C | 0.201 | likely_benign | 0.1717 | benign | -1.648 | Destabilizing | 0.003 | N | 0.393 | neutral | N | 0.43141247 | None | None | N |
| F/D | 0.852 | likely_pathogenic | 0.8071 | pathogenic | -1.718 | Destabilizing | 0.888 | D | 0.631 | neutral | None | None | None | None | N |
| F/E | 0.7968 | likely_pathogenic | 0.7589 | pathogenic | -1.581 | Destabilizing | 0.722 | D | 0.628 | neutral | None | None | None | None | N |
| F/G | 0.7961 | likely_pathogenic | 0.7478 | pathogenic | -2.835 | Highly Destabilizing | 0.722 | D | 0.503 | neutral | None | None | None | None | N |
| F/H | 0.5228 | ambiguous | 0.47 | ambiguous | -1.072 | Destabilizing | 0.818 | D | 0.573 | neutral | None | None | None | None | N |
| F/I | 0.0885 | likely_benign | 0.0786 | benign | -1.274 | Destabilizing | 0.08 | N | 0.263 | neutral | N | 0.414885579 | None | None | N |
| F/K | 0.8062 | likely_pathogenic | 0.771 | pathogenic | -1.911 | Destabilizing | 0.722 | D | 0.621 | neutral | None | None | None | None | N |
| F/L | 0.6105 | likely_pathogenic | 0.5387 | ambiguous | -1.274 | Destabilizing | 0.08 | N | 0.24 | neutral | N | 0.438858517 | None | None | N |
| F/M | 0.253 | likely_benign | 0.2259 | benign | -1.046 | Destabilizing | 0.901 | D | 0.503 | neutral | None | None | None | None | N |
| F/N | 0.5919 | likely_pathogenic | 0.5444 | ambiguous | -2.144 | Highly Destabilizing | 0.901 | D | 0.629 | neutral | None | None | None | None | N |
| F/P | 0.9908 | likely_pathogenic | 0.9882 | pathogenic | -1.667 | Destabilizing | 0.965 | D | 0.625 | neutral | None | None | None | None | N |
| F/Q | 0.6811 | likely_pathogenic | 0.6366 | pathogenic | -2.135 | Highly Destabilizing | 0.901 | D | 0.612 | neutral | None | None | None | None | N |
| F/R | 0.7501 | likely_pathogenic | 0.7131 | pathogenic | -1.298 | Destabilizing | 0.901 | D | 0.626 | neutral | None | None | None | None | N |
| F/S | 0.3538 | ambiguous | 0.2965 | benign | -2.888 | Highly Destabilizing | 0.662 | D | 0.499 | neutral | N | 0.410631766 | None | None | N |
| F/T | 0.3684 | ambiguous | 0.3119 | benign | -2.647 | Highly Destabilizing | 0.345 | N | 0.471 | neutral | None | None | None | None | N |
| F/V | 0.0887 | likely_benign | 0.0789 | benign | -1.667 | Destabilizing | None | N | 0.215 | neutral | N | 0.364899476 | None | None | N |
| F/W | 0.5811 | likely_pathogenic | 0.5203 | ambiguous | -0.29 | Destabilizing | 0.901 | D | 0.538 | neutral | None | None | None | None | N |
| F/Y | 0.1731 | likely_benign | 0.1557 | benign | -0.635 | Destabilizing | 0.001 | N | 0.131 | neutral | N | 0.432105903 | 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.