Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21694 | 65305;65306;65307 | chr2:178584471;178584470;178584469 | chr2:179449198;179449197;179449196 |
| N2AB | 20053 | 60382;60383;60384 | chr2:178584471;178584470;178584469 | chr2:179449198;179449197;179449196 |
| N2A | 19126 | 57601;57602;57603 | chr2:178584471;178584470;178584469 | chr2:179449198;179449197;179449196 |
| N2B | 12629 | 38110;38111;38112 | chr2:178584471;178584470;178584469 | chr2:179449198;179449197;179449196 |
| Novex-1 | 12754 | 38485;38486;38487 | chr2:178584471;178584470;178584469 | chr2:179449198;179449197;179449196 |
| Novex-2 | 12821 | 38686;38687;38688 | chr2:178584471;178584470;178584469 | chr2:179449198;179449197;179449196 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/H | rs369058733  |
-2.912 | 1.0 | D | 0.747 | 0.849 | None | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 1.29249E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| Y/H | rs369058733 |
-2.912 | 1.0 | D | 0.747 | 0.849 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 9.66E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/H | rs369058733 |
-2.912 | 1.0 | D | 0.747 | 0.849 | None | gnomAD-4.0.0 | 5.57923E-06 | None | None | None | None | N | None | 5.34431E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39119E-06 | 0 | 1.60164E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9982 | likely_pathogenic | 0.9977 | pathogenic | -3.187 | Highly Destabilizing | 0.998 | D | 0.794 | deleterious | None | None | None | None | N |
| Y/C | 0.9322 | likely_pathogenic | 0.9171 | pathogenic | -1.599 | Destabilizing | 1.0 | D | 0.85 | deleterious | D | 0.633546522 | None | None | N |
| Y/D | 0.998 | likely_pathogenic | 0.9973 | pathogenic | -3.73 | Highly Destabilizing | 1.0 | D | 0.902 | deleterious | D | 0.649999852 | None | None | N |
| Y/E | 0.9994 | likely_pathogenic | 0.9993 | pathogenic | -3.503 | Highly Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| Y/F | 0.2322 | likely_benign | 0.2017 | benign | -1.298 | Destabilizing | 0.434 | N | 0.394 | neutral | D | 0.573467674 | None | None | N |
| Y/G | 0.9938 | likely_pathogenic | 0.9922 | pathogenic | -3.607 | Highly Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | None | N |
| Y/H | 0.9798 | likely_pathogenic | 0.9753 | pathogenic | -2.499 | Highly Destabilizing | 1.0 | D | 0.747 | deleterious | D | 0.649394439 | None | None | N |
| Y/I | 0.9864 | likely_pathogenic | 0.9838 | pathogenic | -1.77 | Destabilizing | 0.999 | D | 0.782 | deleterious | None | None | None | None | N |
| Y/K | 0.9991 | likely_pathogenic | 0.999 | pathogenic | -2.344 | Highly Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | None | N |
| Y/L | 0.9675 | likely_pathogenic | 0.9622 | pathogenic | -1.77 | Destabilizing | 0.994 | D | 0.724 | prob.delet. | None | None | None | None | N |
| Y/M | 0.9899 | likely_pathogenic | 0.9881 | pathogenic | -1.423 | Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| Y/N | 0.9847 | likely_pathogenic | 0.9811 | pathogenic | -3.229 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | D | 0.649798048 | None | None | N |
| Y/P | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -2.262 | Highly Destabilizing | 1.0 | D | 0.908 | deleterious | None | None | None | None | N |
| Y/Q | 0.9989 | likely_pathogenic | 0.9986 | pathogenic | -2.909 | Highly Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| Y/R | 0.9968 | likely_pathogenic | 0.9964 | pathogenic | -2.257 | Highly Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| Y/S | 0.9923 | likely_pathogenic | 0.99 | pathogenic | -3.474 | Highly Destabilizing | 1.0 | D | 0.868 | deleterious | D | 0.649798048 | None | None | N |
| Y/T | 0.9976 | likely_pathogenic | 0.9968 | pathogenic | -3.12 | Highly Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | N |
| Y/V | 0.9782 | likely_pathogenic | 0.9741 | pathogenic | -2.262 | Highly Destabilizing | 0.997 | D | 0.74 | deleterious | None | None | None | None | N |
| Y/W | 0.8594 | likely_pathogenic | 0.842 | pathogenic | -0.599 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | 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.