Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 125 | 598;599;600 | chr2:178800605;178800604;178800603 | chr2:179665332;179665331;179665330 |
| N2AB | 125 | 598;599;600 | chr2:178800605;178800604;178800603 | chr2:179665332;179665331;179665330 |
| N2A | 125 | 598;599;600 | chr2:178800605;178800604;178800603 | chr2:179665332;179665331;179665330 |
| N2B | 125 | 598;599;600 | chr2:178800605;178800604;178800603 | chr2:179665332;179665331;179665330 |
| Novex-1 | 125 | 598;599;600 | chr2:178800605;178800604;178800603 | chr2:179665332;179665331;179665330 |
| Novex-2 | 125 | 598;599;600 | chr2:178800605;178800604;178800603 | chr2:179665332;179665331;179665330 |
| Novex-3 | 125 | 598;599;600 | chr2:178800605;178800604;178800603 | chr2:179665332;179665331;179665330 |
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/L | rs368101663  |
-0.123 | 0.987 | D | 0.715 | 0.498 | 0.613002003054 | gnomAD-2.1.1 | 7.09E-06 | None | None | None | -1.054(TCAP) | N | None | 8.01E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/L | rs368101663 |
-0.123 | 0.987 | D | 0.715 | 0.498 | 0.613002003054 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | -1.054(TCAP) | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs368101663 |
-0.123 | 0.987 | D | 0.715 | 0.498 | 0.613002003054 | gnomAD-4.0.0 | 1.31413E-05 | None | None | None | -1.054(TCAP) | N | None | 4.82532E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | None | None | 1.0 | D | 0.811 | 0.514 | 0.641369747695 | gnomAD-4.0.0 | 1.59222E-06 | None | None | None | -1.459(TCAP) | N | None | 0 | 0 | None | 0 | 2.77377E-05 | None | 0 | 0 | 0 | 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 | 0.7621 | likely_pathogenic | 0.7815 | pathogenic | -1.863 | Destabilizing | 0.999 | D | 0.719 | prob.delet. | N | 0.521510388 | None | -0.565(TCAP) | N |
| V/C | 0.9649 | likely_pathogenic | 0.9602 | pathogenic | -0.963 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | -1.761(TCAP) | N |
| V/D | 0.9963 | likely_pathogenic | 0.9966 | pathogenic | -2.755 | Highly Destabilizing | 1.0 | D | 0.921 | deleterious | None | None | None | -1.115(TCAP) | N |
| V/E | 0.9905 | likely_pathogenic | 0.9911 | pathogenic | -2.419 | Highly Destabilizing | 1.0 | D | 0.914 | deleterious | D | 0.699935201 | None | -1.3(TCAP) | N |
| V/F | 0.9139 | likely_pathogenic | 0.9042 | pathogenic | -1.035 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | -1.324(TCAP) | N |
| V/G | 0.7931 | likely_pathogenic | 0.8198 | pathogenic | -2.476 | Highly Destabilizing | 1.0 | D | 0.909 | deleterious | D | 0.589140519 | None | -0.424(TCAP) | N |
| V/H | 0.9986 | likely_pathogenic | 0.9985 | pathogenic | -2.569 | Highly Destabilizing | 1.0 | D | 0.932 | deleterious | None | None | None | -0.761(TCAP) | N |
| V/I | 0.2418 | likely_benign | 0.2201 | benign | -0.067 | Destabilizing | 0.996 | D | 0.589 | neutral | None | None | None | -1.054(TCAP) | N |
| V/K | 0.9957 | likely_pathogenic | 0.9959 | pathogenic | -1.255 | Destabilizing | 1.0 | D | 0.916 | deleterious | None | None | None | -1.768(TCAP) | N |
| V/L | 0.8403 | likely_pathogenic | 0.8162 | pathogenic | -0.067 | Destabilizing | 0.987 | D | 0.715 | prob.delet. | D | 0.586980488 | None | -1.054(TCAP) | N |
| V/M | 0.8445 | likely_pathogenic | 0.8254 | pathogenic | -0.327 | Destabilizing | 1.0 | D | 0.811 | deleterious | D | 0.661800579 | None | -1.459(TCAP) | N |
| V/N | 0.9902 | likely_pathogenic | 0.9901 | pathogenic | -2.029 | Highly Destabilizing | 1.0 | D | 0.943 | deleterious | None | None | None | -1.115(TCAP) | N |
| V/P | 0.9979 | likely_pathogenic | 0.9979 | pathogenic | -0.649 | Destabilizing | 1.0 | D | 0.915 | deleterious | None | None | None | -0.882(TCAP) | N |
| V/Q | 0.9917 | likely_pathogenic | 0.992 | pathogenic | -1.582 | Destabilizing | 1.0 | D | 0.942 | deleterious | None | None | None | -1.301(TCAP) | N |
| V/R | 0.9916 | likely_pathogenic | 0.9924 | pathogenic | -1.654 | Destabilizing | 1.0 | D | 0.945 | deleterious | None | None | None | -1.651(TCAP) | N |
| V/S | 0.9327 | likely_pathogenic | 0.9399 | pathogenic | -2.443 | Highly Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | -0.949(TCAP) | N |
| V/T | 0.8623 | likely_pathogenic | 0.8671 | pathogenic | -1.937 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | -1.161(TCAP) | N |
| V/W | 0.9991 | likely_pathogenic | 0.9991 | pathogenic | -1.563 | Destabilizing | 1.0 | D | 0.933 | deleterious | None | None | None | -1.813(TCAP) | N |
| V/Y | 0.991 | likely_pathogenic | 0.9902 | pathogenic | -1.217 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | -1.384(TCAP) | 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.