Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20854 | 62785;62786;62787 | chr2:178589165;178589164;178589163 | chr2:179453892;179453891;179453890 |
| N2AB | 19213 | 57862;57863;57864 | chr2:178589165;178589164;178589163 | chr2:179453892;179453891;179453890 |
| N2A | 18286 | 55081;55082;55083 | chr2:178589165;178589164;178589163 | chr2:179453892;179453891;179453890 |
| N2B | 11789 | 35590;35591;35592 | chr2:178589165;178589164;178589163 | chr2:179453892;179453891;179453890 |
| Novex-1 | 11914 | 35965;35966;35967 | chr2:178589165;178589164;178589163 | chr2:179453892;179453891;179453890 |
| Novex-2 | 11981 | 36166;36167;36168 | chr2:178589165;178589164;178589163 | chr2:179453892;179453891;179453890 |
| 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/M | rs746626221  |
-0.231 | 0.949 | N | 0.53 | 0.228 | 0.596510716227 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/M | rs746626221 |
-0.231 | 0.949 | N | 0.53 | 0.228 | 0.596510716227 | gnomAD-4.0.0 | 1.59205E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43295E-05 | 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 | 0.1888 | likely_benign | 0.2252 | benign | -0.942 | Destabilizing | 0.349 | N | 0.455 | neutral | N | 0.437434365 | None | None | N |
| V/C | 0.7246 | likely_pathogenic | 0.8345 | pathogenic | -0.783 | Destabilizing | 0.996 | D | 0.625 | neutral | None | None | None | None | N |
| V/D | 0.6173 | likely_pathogenic | 0.7338 | pathogenic | -0.415 | Destabilizing | 0.923 | D | 0.642 | neutral | None | None | None | None | N |
| V/E | 0.4212 | ambiguous | 0.5085 | ambiguous | -0.402 | Destabilizing | 0.901 | D | 0.613 | neutral | N | 0.3959876 | None | None | N |
| V/F | 0.2847 | likely_benign | 0.3102 | benign | -0.604 | Destabilizing | 0.961 | D | 0.631 | neutral | None | None | None | None | N |
| V/G | 0.3971 | ambiguous | 0.4855 | ambiguous | -1.232 | Destabilizing | 0.722 | D | 0.62 | neutral | N | 0.515433789 | None | None | N |
| V/H | 0.6389 | likely_pathogenic | 0.7183 | pathogenic | -0.565 | Destabilizing | 0.996 | D | 0.719 | prob.delet. | None | None | None | None | N |
| V/I | 0.0834 | likely_benign | 0.0913 | benign | -0.263 | Destabilizing | 0.415 | N | 0.51 | neutral | None | None | None | None | N |
| V/K | 0.5065 | ambiguous | 0.5652 | pathogenic | -0.75 | Destabilizing | 0.923 | D | 0.623 | neutral | None | None | None | None | N |
| V/L | 0.2547 | likely_benign | 0.3119 | benign | -0.263 | Destabilizing | 0.349 | N | 0.491 | neutral | N | 0.474760602 | None | None | N |
| V/M | 0.169 | likely_benign | 0.2065 | benign | -0.426 | Destabilizing | 0.949 | D | 0.53 | neutral | N | 0.504736792 | None | None | N |
| V/N | 0.3939 | ambiguous | 0.5297 | ambiguous | -0.681 | Destabilizing | 0.923 | D | 0.652 | neutral | None | None | None | None | N |
| V/P | 0.8643 | likely_pathogenic | 0.9211 | pathogenic | -0.454 | Destabilizing | 0.961 | D | 0.65 | neutral | None | None | None | None | N |
| V/Q | 0.3517 | ambiguous | 0.418 | ambiguous | -0.761 | Destabilizing | 0.961 | D | 0.683 | prob.neutral | None | None | None | None | N |
| V/R | 0.4932 | ambiguous | 0.5162 | ambiguous | -0.328 | Destabilizing | 0.923 | D | 0.698 | prob.neutral | None | None | None | None | N |
| V/S | 0.1929 | likely_benign | 0.2607 | benign | -1.214 | Destabilizing | 0.633 | D | 0.563 | neutral | None | None | None | None | N |
| V/T | 0.1132 | likely_benign | 0.1334 | benign | -1.077 | Destabilizing | 0.002 | N | 0.205 | neutral | None | None | None | None | N |
| V/W | 0.8833 | likely_pathogenic | 0.9104 | pathogenic | -0.772 | Destabilizing | 0.996 | D | 0.757 | deleterious | None | None | None | None | N |
| V/Y | 0.6749 | likely_pathogenic | 0.7538 | pathogenic | -0.453 | Destabilizing | 0.961 | D | 0.633 | neutral | 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.