Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3969 | 12130;12131;12132 | chr2:178741328;178741327;178741326 | chr2:179606055;179606054;179606053 |
| N2AB | 3652 | 11179;11180;11181 | chr2:178741328;178741327;178741326 | chr2:179606055;179606054;179606053 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3606 | 11041;11042;11043 | chr2:178741328;178741327;178741326 | chr2:179606055;179606054;179606053 |
| Novex-1 | 3731 | 11416;11417;11418 | chr2:178741328;178741327;178741326 | chr2:179606055;179606054;179606053 |
| Novex-2 | 3798 | 11617;11618;11619 | chr2:178741328;178741327;178741326 | chr2:179606055;179606054;179606053 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs754991360  |
-0.668 | 0.006 | N | 0.206 | 0.101 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| V/I | rs754991360 |
-0.668 | 0.006 | N | 0.206 | 0.101 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/I | rs754991360 |
-0.668 | 0.006 | N | 0.206 | 0.101 | None | gnomAD-4.0.0 | 3.71813E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08551E-06 | 0 | 0 |
| V/L | rs754991360 |
None | 0.114 | D | 0.506 | 0.24 | None | gnomAD-4.0.0 | 8.89428E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.16926E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.6068 | likely_pathogenic | 0.4832 | ambiguous | -1.992 | Destabilizing | 0.645 | D | 0.65 | neutral | D | 0.688915875 | None | None | I |
| V/C | 0.9185 | likely_pathogenic | 0.8949 | pathogenic | -1.201 | Destabilizing | 0.995 | D | 0.705 | prob.neutral | None | None | None | None | I |
| V/D | 0.9578 | likely_pathogenic | 0.9005 | pathogenic | -2.215 | Highly Destabilizing | 0.928 | D | 0.843 | deleterious | D | 0.768262134 | None | None | I |
| V/E | 0.8997 | likely_pathogenic | 0.8134 | pathogenic | -2.118 | Highly Destabilizing | 0.945 | D | 0.835 | deleterious | None | None | None | None | I |
| V/F | 0.4153 | ambiguous | 0.3561 | ambiguous | -1.431 | Destabilizing | 0.864 | D | 0.744 | deleterious | D | 0.689651973 | None | None | I |
| V/G | 0.8026 | likely_pathogenic | 0.6707 | pathogenic | -2.399 | Highly Destabilizing | 0.928 | D | 0.839 | deleterious | D | 0.803541607 | None | None | I |
| V/H | 0.9644 | likely_pathogenic | 0.9404 | pathogenic | -2.02 | Highly Destabilizing | 0.995 | D | 0.824 | deleterious | None | None | None | None | I |
| V/I | 0.079 | likely_benign | 0.0816 | benign | -0.906 | Destabilizing | 0.006 | N | 0.206 | neutral | N | 0.515284917 | None | None | I |
| V/K | 0.9228 | likely_pathogenic | 0.8723 | pathogenic | -1.71 | Destabilizing | 0.894 | D | 0.838 | deleterious | None | None | None | None | I |
| V/L | 0.3474 | ambiguous | 0.3146 | benign | -0.906 | Destabilizing | 0.114 | N | 0.506 | neutral | D | 0.597714033 | None | None | I |
| V/M | 0.2974 | likely_benign | 0.2546 | benign | -0.644 | Destabilizing | 0.332 | N | 0.548 | neutral | None | None | None | None | I |
| V/N | 0.8976 | likely_pathogenic | 0.8079 | pathogenic | -1.592 | Destabilizing | 0.945 | D | 0.839 | deleterious | None | None | None | None | I |
| V/P | 0.9002 | likely_pathogenic | 0.8474 | pathogenic | -1.239 | Destabilizing | 0.981 | D | 0.836 | deleterious | None | None | None | None | I |
| V/Q | 0.91 | likely_pathogenic | 0.8484 | pathogenic | -1.64 | Destabilizing | 0.945 | D | 0.837 | deleterious | None | None | None | None | I |
| V/R | 0.8979 | likely_pathogenic | 0.8384 | pathogenic | -1.307 | Destabilizing | 0.945 | D | 0.834 | deleterious | None | None | None | None | I |
| V/S | 0.8142 | likely_pathogenic | 0.6933 | pathogenic | -2.094 | Highly Destabilizing | 0.945 | D | 0.801 | deleterious | None | None | None | None | I |
| V/T | 0.6589 | likely_pathogenic | 0.5412 | ambiguous | -1.875 | Destabilizing | 0.707 | D | 0.696 | prob.neutral | None | None | None | None | I |
| V/W | 0.9723 | likely_pathogenic | 0.9604 | pathogenic | -1.742 | Destabilizing | 0.995 | D | 0.826 | deleterious | None | None | None | None | I |
| V/Y | 0.9078 | likely_pathogenic | 0.8744 | pathogenic | -1.451 | Destabilizing | 0.945 | D | 0.72 | prob.delet. | None | None | None | None | I |
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.