Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26926 | 81001;81002;81003 | chr2:178565356;178565355;178565354 | chr2:179430083;179430082;179430081 |
| N2AB | 25285 | 76078;76079;76080 | chr2:178565356;178565355;178565354 | chr2:179430083;179430082;179430081 |
| N2A | 24358 | 73297;73298;73299 | chr2:178565356;178565355;178565354 | chr2:179430083;179430082;179430081 |
| N2B | 17861 | 53806;53807;53808 | chr2:178565356;178565355;178565354 | chr2:179430083;179430082;179430081 |
| Novex-1 | 17986 | 54181;54182;54183 | chr2:178565356;178565355;178565354 | chr2:179430083;179430082;179430081 |
| Novex-2 | 18053 | 54382;54383;54384 | chr2:178565356;178565355;178565354 | chr2:179430083;179430082;179430081 |
| 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/L | rs769499232  |
-0.912 | None | N | 0.163 | 0.143 | 0.239901079897 | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 3.89842E-04 | None | 0 | None | 0 | 0 | 0 |
| V/L | rs769499232 |
-0.912 | None | N | 0.163 | 0.143 | 0.239901079897 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 3.86698E-04 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs769499232 |
-0.912 | None | N | 0.163 | 0.143 | 0.239901079897 | gnomAD-4.0.0 | 8.05718E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.8979E-04 | 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 | 0.5794 | likely_pathogenic | 0.4407 | ambiguous | -2.081 | Highly Destabilizing | 0.001 | N | 0.206 | neutral | N | 0.488405489 | None | None | N |
| V/C | 0.7968 | likely_pathogenic | 0.7105 | pathogenic | -1.808 | Destabilizing | 0.951 | D | 0.569 | neutral | None | None | None | None | N |
| V/D | 0.9198 | likely_pathogenic | 0.8616 | pathogenic | -2.638 | Highly Destabilizing | 0.716 | D | 0.624 | neutral | None | None | None | None | N |
| V/E | 0.7788 | likely_pathogenic | 0.7058 | pathogenic | -2.54 | Highly Destabilizing | 0.351 | N | 0.564 | neutral | N | 0.505068167 | None | None | N |
| V/F | 0.3041 | likely_benign | 0.2243 | benign | -1.465 | Destabilizing | 0.716 | D | 0.603 | neutral | None | None | None | None | N |
| V/G | 0.5924 | likely_pathogenic | 0.4758 | ambiguous | -2.508 | Highly Destabilizing | 0.002 | N | 0.433 | neutral | D | 0.533768259 | None | None | N |
| V/H | 0.8661 | likely_pathogenic | 0.7843 | pathogenic | -2.124 | Highly Destabilizing | 0.983 | D | 0.587 | neutral | None | None | None | None | N |
| V/I | 0.0747 | likely_benign | 0.0661 | benign | -0.944 | Destabilizing | 0.101 | N | 0.466 | neutral | N | 0.482900083 | None | None | N |
| V/K | 0.7257 | likely_pathogenic | 0.6565 | pathogenic | -1.885 | Destabilizing | 0.418 | N | 0.565 | neutral | None | None | None | None | N |
| V/L | 0.1802 | likely_benign | 0.135 | benign | -0.944 | Destabilizing | None | N | 0.163 | neutral | N | 0.492423643 | None | None | N |
| V/M | 0.2071 | likely_benign | 0.1403 | benign | -0.916 | Destabilizing | 0.716 | D | 0.579 | neutral | None | None | None | None | N |
| V/N | 0.7463 | likely_pathogenic | 0.5973 | pathogenic | -1.954 | Destabilizing | 0.716 | D | 0.614 | neutral | None | None | None | None | N |
| V/P | 0.9905 | likely_pathogenic | 0.9836 | pathogenic | -1.292 | Destabilizing | 0.836 | D | 0.579 | neutral | None | None | None | None | N |
| V/Q | 0.685 | likely_pathogenic | 0.6003 | pathogenic | -2.01 | Highly Destabilizing | 0.836 | D | 0.585 | neutral | None | None | None | None | N |
| V/R | 0.6613 | likely_pathogenic | 0.61 | pathogenic | -1.427 | Destabilizing | 0.716 | D | 0.603 | neutral | None | None | None | None | N |
| V/S | 0.671 | likely_pathogenic | 0.5029 | ambiguous | -2.51 | Highly Destabilizing | 0.264 | N | 0.555 | neutral | None | None | None | None | N |
| V/T | 0.492 | ambiguous | 0.299 | benign | -2.29 | Highly Destabilizing | 0.002 | N | 0.242 | neutral | None | None | None | None | N |
| V/W | 0.8959 | likely_pathogenic | 0.8399 | pathogenic | -1.827 | Destabilizing | 0.983 | D | 0.598 | neutral | None | None | None | None | N |
| V/Y | 0.7472 | likely_pathogenic | 0.6433 | pathogenic | -1.519 | Destabilizing | 0.836 | D | 0.611 | 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.