Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20186 | 60781;60782;60783 | chr2:178591169;178591168;178591167 | chr2:179455896;179455895;179455894 |
| N2AB | 18545 | 55858;55859;55860 | chr2:178591169;178591168;178591167 | chr2:179455896;179455895;179455894 |
| N2A | 17618 | 53077;53078;53079 | chr2:178591169;178591168;178591167 | chr2:179455896;179455895;179455894 |
| N2B | 11121 | 33586;33587;33588 | chr2:178591169;178591168;178591167 | chr2:179455896;179455895;179455894 |
| Novex-1 | 11246 | 33961;33962;33963 | chr2:178591169;178591168;178591167 | chr2:179455896;179455895;179455894 |
| Novex-2 | 11313 | 34162;34163;34164 | chr2:178591169;178591168;178591167 | chr2:179455896;179455895;179455894 |
| 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/A | rs768019616  |
-1.737 | 0.955 | N | 0.567 | 0.331 | 0.270447802918 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 0 | 0 |
| P/R | rs746586306 |
-0.683 | 0.997 | N | 0.808 | 0.403 | 0.402471007487 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| P/R | rs746586306 |
-0.683 | 0.997 | N | 0.808 | 0.403 | 0.402471007487 | gnomAD-4.0.0 | 1.59211E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85982E-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 | 0.0934 | likely_benign | 0.0989 | benign | -1.648 | Destabilizing | 0.955 | D | 0.567 | neutral | N | 0.419605461 | None | None | N |
| P/C | 0.6667 | likely_pathogenic | 0.6643 | pathogenic | -0.908 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| P/D | 0.6862 | likely_pathogenic | 0.7166 | pathogenic | -2.186 | Highly Destabilizing | 0.999 | D | 0.786 | deleterious | None | None | None | None | N |
| P/E | 0.4347 | ambiguous | 0.4595 | ambiguous | -2.186 | Highly Destabilizing | 0.998 | D | 0.78 | deleterious | None | None | None | None | N |
| P/F | 0.8418 | likely_pathogenic | 0.8485 | pathogenic | -1.341 | Destabilizing | 0.999 | D | 0.783 | deleterious | None | None | None | None | N |
| P/G | 0.4742 | ambiguous | 0.5044 | ambiguous | -1.963 | Destabilizing | 0.998 | D | 0.74 | deleterious | None | None | None | None | N |
| P/H | 0.4726 | ambiguous | 0.5184 | ambiguous | -1.669 | Destabilizing | 1.0 | D | 0.781 | deleterious | N | 0.50626444 | None | None | N |
| P/I | 0.6411 | likely_pathogenic | 0.6343 | pathogenic | -0.859 | Destabilizing | 0.99 | D | 0.727 | prob.delet. | None | None | None | None | N |
| P/K | 0.6438 | likely_pathogenic | 0.6729 | pathogenic | -1.389 | Destabilizing | 0.998 | D | 0.78 | deleterious | None | None | None | None | N |
| P/L | 0.2784 | likely_benign | 0.2965 | benign | -0.859 | Destabilizing | 0.987 | D | 0.723 | prob.delet. | N | 0.471826538 | None | None | N |
| P/M | 0.5444 | ambiguous | 0.5491 | ambiguous | -0.493 | Destabilizing | 0.999 | D | 0.795 | deleterious | None | None | None | None | N |
| P/N | 0.5783 | likely_pathogenic | 0.6003 | pathogenic | -1.195 | Destabilizing | 0.999 | D | 0.805 | deleterious | None | None | None | None | N |
| P/Q | 0.3664 | ambiguous | 0.4058 | ambiguous | -1.396 | Destabilizing | 0.999 | D | 0.802 | deleterious | None | None | None | None | N |
| P/R | 0.4728 | ambiguous | 0.512 | ambiguous | -0.84 | Destabilizing | 0.997 | D | 0.808 | deleterious | N | 0.488313397 | None | None | N |
| P/S | 0.1807 | likely_benign | 0.193 | benign | -1.582 | Destabilizing | 0.997 | D | 0.777 | deleterious | N | 0.464393601 | None | None | N |
| P/T | 0.1825 | likely_benign | 0.1964 | benign | -1.493 | Destabilizing | 0.993 | D | 0.715 | prob.delet. | N | 0.520327028 | None | None | N |
| P/V | 0.4163 | ambiguous | 0.4058 | ambiguous | -1.091 | Destabilizing | 0.289 | N | 0.48 | neutral | None | None | None | None | N |
| P/W | 0.878 | likely_pathogenic | 0.8771 | pathogenic | -1.643 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| P/Y | 0.7643 | likely_pathogenic | 0.7692 | pathogenic | -1.361 | Destabilizing | 0.999 | D | 0.778 | 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.