Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23128 | 69607;69608;69609 | chr2:178576953;178576952;178576951 | chr2:179441680;179441679;179441678 |
| N2AB | 21487 | 64684;64685;64686 | chr2:178576953;178576952;178576951 | chr2:179441680;179441679;179441678 |
| N2A | 20560 | 61903;61904;61905 | chr2:178576953;178576952;178576951 | chr2:179441680;179441679;179441678 |
| N2B | 14063 | 42412;42413;42414 | chr2:178576953;178576952;178576951 | chr2:179441680;179441679;179441678 |
| Novex-1 | 14188 | 42787;42788;42789 | chr2:178576953;178576952;178576951 | chr2:179441680;179441679;179441678 |
| Novex-2 | 14255 | 42988;42989;42990 | chr2:178576953;178576952;178576951 | chr2:179441680;179441679;179441678 |
| 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/Y | rs72646882  |
-0.373 | 0.999 | D | 0.859 | 0.472 | None | gnomAD-2.1.1 | 7.51476E-04 | None | None | None | None | N | None | 7.89583E-03 | 4.81123E-04 | None | 0 | 0 | None | 0 | None | 0 | 7.84E-06 | 1.40805E-04 |
| S/Y | rs72646882 |
-0.373 | 0.999 | D | 0.859 | 0.472 | None | gnomAD-3.1.2 | 2.24932E-03 | None | None | None | None | N | None | 7.91697E-03 | 4.58595E-04 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 2.39464E-03 |
| S/Y | rs72646882 |
-0.373 | 0.999 | D | 0.859 | 0.472 | None | 1000 genomes | 1.39776E-03 | None | None | None | None | N | None | 5.3E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| S/Y | rs72646882 |
-0.373 | 0.999 | D | 0.859 | 0.472 | None | gnomAD-4.0.0 | 4.15914E-04 | None | None | None | None | N | None | 7.90688E-03 | 4.83349E-04 | None | 0 | 0 | None | 0 | 3.30579E-04 | 3.39131E-06 | 1.09849E-05 | 6.72495E-04 |
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 | 0.3359 | likely_benign | 0.29 | benign | -0.57 | Destabilizing | 0.994 | D | 0.589 | neutral | N | 0.517092354 | None | None | N |
| S/C | 0.3664 | ambiguous | 0.3229 | benign | -0.382 | Destabilizing | 1.0 | D | 0.801 | deleterious | D | 0.543959248 | None | None | N |
| S/D | 0.9707 | likely_pathogenic | 0.9628 | pathogenic | -0.384 | Destabilizing | 0.998 | D | 0.799 | deleterious | None | None | None | None | N |
| S/E | 0.9884 | likely_pathogenic | 0.9859 | pathogenic | -0.269 | Destabilizing | 0.998 | D | 0.796 | deleterious | None | None | None | None | N |
| S/F | 0.9575 | likely_pathogenic | 0.9454 | pathogenic | -0.424 | Destabilizing | 0.999 | D | 0.858 | deleterious | D | 0.550542614 | None | None | N |
| S/G | 0.35 | ambiguous | 0.2869 | benign | -0.928 | Destabilizing | 0.998 | D | 0.691 | prob.delet. | None | None | None | None | N |
| S/H | 0.973 | likely_pathogenic | 0.9693 | pathogenic | -1.319 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| S/I | 0.8977 | likely_pathogenic | 0.8645 | pathogenic | 0.307 | Stabilizing | 0.999 | D | 0.857 | deleterious | None | None | None | None | N |
| S/K | 0.9974 | likely_pathogenic | 0.9971 | pathogenic | -0.339 | Destabilizing | 0.998 | D | 0.789 | deleterious | None | None | None | None | N |
| S/L | 0.6357 | likely_pathogenic | 0.5931 | pathogenic | 0.307 | Stabilizing | 0.999 | D | 0.817 | deleterious | None | None | None | None | N |
| S/M | 0.7143 | likely_pathogenic | 0.666 | pathogenic | 0.207 | Stabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| S/N | 0.8771 | likely_pathogenic | 0.8491 | pathogenic | -0.647 | Destabilizing | 0.998 | D | 0.795 | deleterious | None | None | None | None | N |
| S/P | 0.9878 | likely_pathogenic | 0.9842 | pathogenic | 0.052 | Stabilizing | 0.999 | D | 0.871 | deleterious | N | 0.507292985 | None | None | N |
| S/Q | 0.985 | likely_pathogenic | 0.9826 | pathogenic | -0.527 | Destabilizing | 0.999 | D | 0.854 | deleterious | None | None | None | None | N |
| S/R | 0.9963 | likely_pathogenic | 0.996 | pathogenic | -0.579 | Destabilizing | 0.999 | D | 0.863 | deleterious | None | None | None | None | N |
| S/T | 0.1175 | likely_benign | 0.1171 | benign | -0.491 | Destabilizing | 0.997 | D | 0.714 | prob.delet. | N | 0.495126985 | None | None | N |
| S/V | 0.8051 | likely_pathogenic | 0.755 | pathogenic | 0.052 | Stabilizing | 0.999 | D | 0.869 | deleterious | None | None | None | None | N |
| S/W | 0.9667 | likely_pathogenic | 0.9629 | pathogenic | -0.561 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| S/Y | 0.9496 | likely_pathogenic | 0.946 | pathogenic | -0.173 | Destabilizing | 0.999 | D | 0.859 | deleterious | D | 0.562316993 | 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.