Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19860 | 59803;59804;59805 | chr2:178592427;178592426;178592425 | chr2:179457154;179457153;179457152 |
| N2AB | 18219 | 54880;54881;54882 | chr2:178592427;178592426;178592425 | chr2:179457154;179457153;179457152 |
| N2A | 17292 | 52099;52100;52101 | chr2:178592427;178592426;178592425 | chr2:179457154;179457153;179457152 |
| N2B | 10795 | 32608;32609;32610 | chr2:178592427;178592426;178592425 | chr2:179457154;179457153;179457152 |
| Novex-1 | 10920 | 32983;32984;32985 | chr2:178592427;178592426;178592425 | chr2:179457154;179457153;179457152 |
| Novex-2 | 10987 | 33184;33185;33186 | chr2:178592427;178592426;178592425 | chr2:179457154;179457153;179457152 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/D | rs757011726  |
-1.206 | 0.999 | D | 0.548 | 0.204 | 0.476832112026 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| E/D | rs757011726 |
-1.206 | 0.999 | D | 0.548 | 0.204 | 0.476832112026 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/D | rs757011726 |
-1.206 | 0.999 | D | 0.548 | 0.204 | 0.476832112026 | gnomAD-4.0.0 | 6.57488E-06 | None | None | None | None | N | None | 2.41278E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/K | None | None | 0.999 | N | 0.667 | 0.397 | 0.411001663086 | gnomAD-4.0.0 | 2.73746E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59842E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.2856 | likely_benign | 0.2791 | benign | -0.547 | Destabilizing | 0.999 | D | 0.71 | prob.delet. | D | 0.523650627 | None | None | N |
| E/C | 0.8773 | likely_pathogenic | 0.8779 | pathogenic | -0.037 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| E/D | 0.3728 | ambiguous | 0.3634 | ambiguous | -0.87 | Destabilizing | 0.999 | D | 0.548 | neutral | D | 0.525690855 | None | None | N |
| E/F | 0.9169 | likely_pathogenic | 0.9182 | pathogenic | -0.697 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| E/G | 0.432 | ambiguous | 0.4579 | ambiguous | -0.808 | Destabilizing | 1.0 | D | 0.747 | deleterious | N | 0.489152731 | None | None | N |
| E/H | 0.6495 | likely_pathogenic | 0.6597 | pathogenic | -1.004 | Destabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | N |
| E/I | 0.5183 | ambiguous | 0.4993 | ambiguous | 0.127 | Stabilizing | 1.0 | D | 0.846 | deleterious | None | None | None | None | N |
| E/K | 0.2554 | likely_benign | 0.2535 | benign | -0.043 | Destabilizing | 0.999 | D | 0.667 | neutral | N | 0.491287492 | None | None | N |
| E/L | 0.6716 | likely_pathogenic | 0.6724 | pathogenic | 0.127 | Stabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| E/M | 0.5922 | likely_pathogenic | 0.5868 | pathogenic | 0.562 | Stabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| E/N | 0.4999 | ambiguous | 0.4818 | ambiguous | -0.291 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| E/P | 0.995 | likely_pathogenic | 0.9963 | pathogenic | -0.076 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | N |
| E/Q | 0.1425 | likely_benign | 0.1417 | benign | -0.261 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | N | 0.48746054 | None | None | N |
| E/R | 0.4105 | ambiguous | 0.4248 | ambiguous | -0.073 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| E/S | 0.2968 | likely_benign | 0.2937 | benign | -0.522 | Destabilizing | 0.999 | D | 0.725 | prob.delet. | None | None | None | None | N |
| E/T | 0.2508 | likely_benign | 0.2477 | benign | -0.309 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| E/V | 0.3068 | likely_benign | 0.2929 | benign | -0.076 | Destabilizing | 1.0 | D | 0.829 | deleterious | N | 0.509625324 | None | None | N |
| E/W | 0.9658 | likely_pathogenic | 0.9696 | pathogenic | -0.649 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | N |
| E/Y | 0.8678 | likely_pathogenic | 0.8682 | pathogenic | -0.467 | Destabilizing | 1.0 | D | 0.826 | 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.