Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22283 | 67072;67073;67074 | chr2:178580532;178580531;178580530 | chr2:179445259;179445258;179445257 |
| N2AB | 20642 | 62149;62150;62151 | chr2:178580532;178580531;178580530 | chr2:179445259;179445258;179445257 |
| N2A | 19715 | 59368;59369;59370 | chr2:178580532;178580531;178580530 | chr2:179445259;179445258;179445257 |
| N2B | 13218 | 39877;39878;39879 | chr2:178580532;178580531;178580530 | chr2:179445259;179445258;179445257 |
| Novex-1 | 13343 | 40252;40253;40254 | chr2:178580532;178580531;178580530 | chr2:179445259;179445258;179445257 |
| Novex-2 | 13410 | 40453;40454;40455 | chr2:178580532;178580531;178580530 | chr2:179445259;179445258;179445257 |
| 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/A | rs1246688280  |
-1.719 | 0.025 | N | 0.421 | 0.121 | 0.439551795455 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| V/A | rs1246688280 |
-1.719 | 0.025 | N | 0.421 | 0.121 | 0.439551795455 | gnomAD-4.0.0 | 1.59361E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86185E-06 | 0 | 0 |
| V/I | rs554828165 |
0.03 | 0.773 | N | 0.621 | 0.195 | 0.543734688498 | gnomAD-2.1.1 | 2.83E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 2.29028E-04 | None | 0 | 0 | 0 |
| V/I | rs554828165 |
0.03 | 0.773 | N | 0.621 | 0.195 | 0.543734688498 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.13736E-04 | 0 |
| V/I | rs554828165 |
0.03 | 0.773 | N | 0.621 | 0.195 | 0.543734688498 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| V/I | rs554828165 |
0.03 | 0.773 | N | 0.621 | 0.195 | 0.543734688498 | gnomAD-4.0.0 | 1.4261E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.19688E-04 | 4.80677E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.7939 | likely_pathogenic | 0.7707 | pathogenic | -1.736 | Destabilizing | 0.025 | N | 0.421 | neutral | N | 0.464539956 | None | None | I |
| V/C | 0.9128 | likely_pathogenic | 0.9064 | pathogenic | -1.243 | Destabilizing | 0.997 | D | 0.774 | deleterious | None | None | None | None | I |
| V/D | 0.9976 | likely_pathogenic | 0.9968 | pathogenic | -1.819 | Destabilizing | 0.987 | D | 0.859 | deleterious | None | None | None | None | I |
| V/E | 0.9929 | likely_pathogenic | 0.9907 | pathogenic | -1.644 | Destabilizing | 0.967 | D | 0.816 | deleterious | N | 0.492322379 | None | None | I |
| V/F | 0.8136 | likely_pathogenic | 0.761 | pathogenic | -1.076 | Destabilizing | 0.987 | D | 0.765 | deleterious | None | None | None | None | I |
| V/G | 0.9374 | likely_pathogenic | 0.9217 | pathogenic | -2.199 | Highly Destabilizing | 0.935 | D | 0.797 | deleterious | N | 0.455860379 | None | None | I |
| V/H | 0.9962 | likely_pathogenic | 0.9948 | pathogenic | -1.61 | Destabilizing | 0.999 | D | 0.86 | deleterious | None | None | None | None | I |
| V/I | 0.1169 | likely_benign | 0.1089 | benign | -0.48 | Destabilizing | 0.773 | D | 0.621 | neutral | N | 0.491091839 | None | None | I |
| V/K | 0.9936 | likely_pathogenic | 0.992 | pathogenic | -1.407 | Destabilizing | 0.975 | D | 0.819 | deleterious | None | None | None | None | I |
| V/L | 0.6694 | likely_pathogenic | 0.6257 | pathogenic | -0.48 | Destabilizing | 0.63 | D | 0.705 | prob.neutral | N | 0.467924247 | None | None | I |
| V/M | 0.7257 | likely_pathogenic | 0.6765 | pathogenic | -0.507 | Destabilizing | 0.996 | D | 0.739 | prob.delet. | None | None | None | None | I |
| V/N | 0.9887 | likely_pathogenic | 0.985 | pathogenic | -1.647 | Destabilizing | 0.987 | D | 0.858 | deleterious | None | None | None | None | I |
| V/P | 0.9947 | likely_pathogenic | 0.9929 | pathogenic | -0.87 | Destabilizing | 0.987 | D | 0.833 | deleterious | None | None | None | None | I |
| V/Q | 0.9868 | likely_pathogenic | 0.984 | pathogenic | -1.549 | Destabilizing | 0.987 | D | 0.837 | deleterious | None | None | None | None | I |
| V/R | 0.9859 | likely_pathogenic | 0.9829 | pathogenic | -1.171 | Destabilizing | 0.987 | D | 0.849 | deleterious | None | None | None | None | I |
| V/S | 0.9295 | likely_pathogenic | 0.9154 | pathogenic | -2.266 | Highly Destabilizing | 0.95 | D | 0.773 | deleterious | None | None | None | None | I |
| V/T | 0.8767 | likely_pathogenic | 0.8555 | pathogenic | -1.939 | Destabilizing | 0.916 | D | 0.704 | prob.neutral | None | None | None | None | I |
| V/W | 0.9976 | likely_pathogenic | 0.9968 | pathogenic | -1.4 | Destabilizing | 0.999 | D | 0.836 | deleterious | None | None | None | None | I |
| V/Y | 0.9841 | likely_pathogenic | 0.9798 | pathogenic | -1.023 | Destabilizing | 0.996 | D | 0.757 | deleterious | 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.