Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21775 | 65548;65549;65550 | chr2:178583859;178583858;178583857 | chr2:179448586;179448585;179448584 |
| N2AB | 20134 | 60625;60626;60627 | chr2:178583859;178583858;178583857 | chr2:179448586;179448585;179448584 |
| N2A | 19207 | 57844;57845;57846 | chr2:178583859;178583858;178583857 | chr2:179448586;179448585;179448584 |
| N2B | 12710 | 38353;38354;38355 | chr2:178583859;178583858;178583857 | chr2:179448586;179448585;179448584 |
| Novex-1 | 12835 | 38728;38729;38730 | chr2:178583859;178583858;178583857 | chr2:179448586;179448585;179448584 |
| Novex-2 | 12902 | 38929;38930;38931 | chr2:178583859;178583858;178583857 | chr2:179448586;179448585;179448584 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/F | None | None | 1.0 | N | 0.784 | 0.405 | 0.667640585422 | gnomAD-4.0.0 | 4.8259E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.66371E-06 | 0 | 0 |
| S/T | rs2048324718  |
None | 0.999 | N | 0.609 | 0.303 | 0.315609569513 | gnomAD-4.0.0 | 1.60846E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.88757E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1809 | likely_benign | 0.1444 | benign | -0.769 | Destabilizing | 0.997 | D | 0.543 | neutral | N | 0.504570929 | None | None | N |
| S/C | 0.1792 | likely_benign | 0.1526 | benign | -0.695 | Destabilizing | 1.0 | D | 0.765 | deleterious | N | 0.479334956 | None | None | N |
| S/D | 0.78 | likely_pathogenic | 0.7498 | pathogenic | -0.724 | Destabilizing | 0.999 | D | 0.607 | neutral | None | None | None | None | N |
| S/E | 0.8422 | likely_pathogenic | 0.8155 | pathogenic | -0.677 | Destabilizing | 0.999 | D | 0.613 | neutral | None | None | None | None | N |
| S/F | 0.4992 | ambiguous | 0.4427 | ambiguous | -0.824 | Destabilizing | 1.0 | D | 0.784 | deleterious | N | 0.472080028 | None | None | N |
| S/G | 0.2365 | likely_benign | 0.1926 | benign | -1.056 | Destabilizing | 0.999 | D | 0.628 | neutral | None | None | None | None | N |
| S/H | 0.4508 | ambiguous | 0.4333 | ambiguous | -1.491 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| S/I | 0.5001 | ambiguous | 0.4161 | ambiguous | -0.098 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| S/K | 0.8149 | likely_pathogenic | 0.7711 | pathogenic | -0.677 | Destabilizing | 0.999 | D | 0.601 | neutral | None | None | None | None | N |
| S/L | 0.2757 | likely_benign | 0.2239 | benign | -0.098 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| S/M | 0.3967 | ambiguous | 0.3269 | benign | 0.054 | Stabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | N |
| S/N | 0.3255 | likely_benign | 0.2745 | benign | -0.841 | Destabilizing | 0.999 | D | 0.611 | neutral | None | None | None | None | N |
| S/P | 0.9581 | likely_pathogenic | 0.9613 | pathogenic | -0.287 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | N | 0.483854407 | None | None | N |
| S/Q | 0.6761 | likely_pathogenic | 0.6338 | pathogenic | -0.942 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| S/R | 0.7387 | likely_pathogenic | 0.6995 | pathogenic | -0.648 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| S/T | 0.091 | likely_benign | 0.0785 | benign | -0.769 | Destabilizing | 0.999 | D | 0.609 | neutral | N | 0.409388467 | None | None | N |
| S/V | 0.4451 | ambiguous | 0.3661 | ambiguous | -0.287 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| S/W | 0.5663 | likely_pathogenic | 0.5746 | pathogenic | -0.842 | Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | N |
| S/Y | 0.3926 | ambiguous | 0.3709 | ambiguous | -0.533 | Destabilizing | 1.0 | D | 0.793 | deleterious | N | 0.514691922 | 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.