Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30917 | 92974;92975;92976 | chr2:178548877;178548876;178548875 | chr2:179413604;179413603;179413602 |
| N2AB | 29276 | 88051;88052;88053 | chr2:178548877;178548876;178548875 | chr2:179413604;179413603;179413602 |
| N2A | 28349 | 85270;85271;85272 | chr2:178548877;178548876;178548875 | chr2:179413604;179413603;179413602 |
| N2B | 21852 | 65779;65780;65781 | chr2:178548877;178548876;178548875 | chr2:179413604;179413603;179413602 |
| Novex-1 | 21977 | 66154;66155;66156 | chr2:178548877;178548876;178548875 | chr2:179413604;179413603;179413602 |
| Novex-2 | 22044 | 66355;66356;66357 | chr2:178548877;178548876;178548875 | chr2:179413604;179413603;179413602 |
| 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 | rs748545482  |
-0.779 | 0.003 | N | 0.143 | 0.153 | 0.445410361449 | gnomAD-2.1.1 | 2.81E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 2.28743E-04 | None | 0 | 0 | 0 |
| V/A | rs748545482 |
-0.779 | 0.003 | N | 0.143 | 0.153 | 0.445410361449 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07383E-04 | 0 |
| V/A | rs748545482 |
-0.779 | 0.003 | N | 0.143 | 0.153 | 0.445410361449 | gnomAD-4.0.0 | 2.29297E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.22946E-05 | None | 0 | 0 | 8.47588E-07 | 3.73298E-04 | 1.60108E-05 |
| V/I | None | None | 0.003 | N | 0.227 | 0.065 | 0.355865052028 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 | 0.1004 | likely_benign | 0.1026 | benign | -0.351 | Destabilizing | 0.003 | N | 0.143 | neutral | N | 0.446627064 | None | None | N |
| V/C | 0.6077 | likely_pathogenic | 0.622 | pathogenic | -0.571 | Destabilizing | 0.991 | D | 0.319 | neutral | None | None | None | None | N |
| V/D | 0.2988 | likely_benign | 0.2789 | benign | -0.196 | Destabilizing | 0.877 | D | 0.631 | neutral | N | 0.429081454 | None | None | N |
| V/E | 0.1719 | likely_benign | 0.1562 | benign | -0.325 | Destabilizing | 0.824 | D | 0.478 | neutral | None | None | None | None | N |
| V/F | 0.1829 | likely_benign | 0.1843 | benign | -0.705 | Destabilizing | 0.779 | D | 0.422 | neutral | N | 0.471082792 | None | None | N |
| V/G | 0.1857 | likely_benign | 0.1776 | benign | -0.454 | Destabilizing | 0.335 | N | 0.439 | neutral | N | 0.44127996 | None | None | N |
| V/H | 0.4781 | ambiguous | 0.4629 | ambiguous | -0.078 | Destabilizing | 0.991 | D | 0.507 | neutral | None | None | None | None | N |
| V/I | 0.0673 | likely_benign | 0.0703 | benign | -0.237 | Destabilizing | 0.003 | N | 0.227 | neutral | N | 0.451976956 | None | None | N |
| V/K | 0.2376 | likely_benign | 0.2265 | benign | -0.236 | Destabilizing | 0.824 | D | 0.471 | neutral | None | None | None | None | N |
| V/L | 0.1471 | likely_benign | 0.1517 | benign | -0.237 | Destabilizing | 0.001 | N | 0.064 | neutral | N | 0.424019564 | None | None | N |
| V/M | 0.0924 | likely_benign | 0.0923 | benign | -0.255 | Destabilizing | 0.824 | D | 0.438 | neutral | None | None | None | None | N |
| V/N | 0.1914 | likely_benign | 0.194 | benign | 0.033 | Stabilizing | 0.905 | D | 0.56 | neutral | None | None | None | None | N |
| V/P | 0.833 | likely_pathogenic | 0.8438 | pathogenic | -0.241 | Destabilizing | 0.905 | D | 0.592 | neutral | None | None | None | None | N |
| V/Q | 0.209 | likely_benign | 0.1975 | benign | -0.242 | Destabilizing | 0.905 | D | 0.52 | neutral | None | None | None | None | N |
| V/R | 0.2332 | likely_benign | 0.2368 | benign | 0.266 | Stabilizing | 0.905 | D | 0.619 | neutral | None | None | None | None | N |
| V/S | 0.1348 | likely_benign | 0.1315 | benign | -0.319 | Destabilizing | 0.4 | N | 0.398 | neutral | None | None | None | None | N |
| V/T | 0.0899 | likely_benign | 0.0883 | benign | -0.349 | Destabilizing | 0.571 | D | 0.279 | neutral | None | None | None | None | N |
| V/W | 0.7904 | likely_pathogenic | 0.7806 | pathogenic | -0.762 | Destabilizing | 0.991 | D | 0.623 | neutral | None | None | None | None | N |
| V/Y | 0.5129 | ambiguous | 0.5078 | ambiguous | -0.443 | Destabilizing | 0.905 | D | 0.439 | 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.