Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31703 | 95332;95333;95334 | chr2:178546224;178546223;178546222 | chr2:179410951;179410950;179410949 |
| N2AB | 30062 | 90409;90410;90411 | chr2:178546224;178546223;178546222 | chr2:179410951;179410950;179410949 |
| N2A | 29135 | 87628;87629;87630 | chr2:178546224;178546223;178546222 | chr2:179410951;179410950;179410949 |
| N2B | 22638 | 68137;68138;68139 | chr2:178546224;178546223;178546222 | chr2:179410951;179410950;179410949 |
| Novex-1 | 22763 | 68512;68513;68514 | chr2:178546224;178546223;178546222 | chr2:179410951;179410950;179410949 |
| Novex-2 | 22830 | 68713;68714;68715 | chr2:178546224;178546223;178546222 | chr2:179410951;179410950;179410949 |
| 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 | rs757333745  |
-0.555 | 0.981 | N | 0.534 | 0.256 | 0.477838726898 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.7E-05 | 0 | 0 |
| V/I | rs757333745 |
-0.555 | 0.981 | N | 0.534 | 0.256 | 0.477838726898 | gnomAD-4.0.0 | 6.86056E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87857E-05 | 0 | 0 | 0 | 0 |
| V/L | rs757333745 |
None | 0.434 | N | 0.297 | 0.144 | None | gnomAD-4.0.0 | 4.11633E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.40973E-06 | 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 | 0.8171 | likely_pathogenic | 0.8647 | pathogenic | -1.946 | Destabilizing | 0.998 | D | 0.607 | neutral | N | 0.50122683 | None | None | N |
| V/C | 0.933 | likely_pathogenic | 0.9468 | pathogenic | -1.447 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| V/D | 0.9985 | likely_pathogenic | 0.9987 | pathogenic | -2.262 | Highly Destabilizing | 1.0 | D | 0.861 | deleterious | D | 0.524611004 | None | None | N |
| V/E | 0.9952 | likely_pathogenic | 0.9956 | pathogenic | -2.075 | Highly Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| V/F | 0.8844 | likely_pathogenic | 0.9195 | pathogenic | -1.158 | Destabilizing | 0.999 | D | 0.827 | deleterious | N | 0.511987251 | None | None | N |
| V/G | 0.8947 | likely_pathogenic | 0.9152 | pathogenic | -2.467 | Highly Destabilizing | 1.0 | D | 0.865 | deleterious | D | 0.524611004 | None | None | N |
| V/H | 0.9982 | likely_pathogenic | 0.9985 | pathogenic | -2.163 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| V/I | 0.1402 | likely_benign | 0.1776 | benign | -0.513 | Destabilizing | 0.981 | D | 0.534 | neutral | N | 0.466140275 | None | None | N |
| V/K | 0.9959 | likely_pathogenic | 0.9959 | pathogenic | -1.681 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| V/L | 0.5723 | likely_pathogenic | 0.664 | pathogenic | -0.513 | Destabilizing | 0.434 | N | 0.297 | neutral | N | 0.476991099 | None | None | N |
| V/M | 0.7581 | likely_pathogenic | 0.8378 | pathogenic | -0.482 | Destabilizing | 0.999 | D | 0.763 | deleterious | None | None | None | None | N |
| V/N | 0.9935 | likely_pathogenic | 0.995 | pathogenic | -1.883 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| V/P | 0.9941 | likely_pathogenic | 0.9943 | pathogenic | -0.961 | Destabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | N |
| V/Q | 0.9935 | likely_pathogenic | 0.9943 | pathogenic | -1.77 | Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | N |
| V/R | 0.9922 | likely_pathogenic | 0.9919 | pathogenic | -1.446 | Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| V/S | 0.9731 | likely_pathogenic | 0.9829 | pathogenic | -2.53 | Highly Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| V/T | 0.8964 | likely_pathogenic | 0.9278 | pathogenic | -2.199 | Highly Destabilizing | 0.998 | D | 0.649 | neutral | None | None | None | None | N |
| V/W | 0.9984 | likely_pathogenic | 0.999 | pathogenic | -1.64 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| V/Y | 0.992 | likely_pathogenic | 0.994 | pathogenic | -1.252 | Destabilizing | 1.0 | D | 0.812 | deleterious | 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.