Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21014 | 63265;63266;63267 | chr2:178588685;178588684;178588683 | chr2:179453412;179453411;179453410 |
| N2AB | 19373 | 58342;58343;58344 | chr2:178588685;178588684;178588683 | chr2:179453412;179453411;179453410 |
| N2A | 18446 | 55561;55562;55563 | chr2:178588685;178588684;178588683 | chr2:179453412;179453411;179453410 |
| N2B | 11949 | 36070;36071;36072 | chr2:178588685;178588684;178588683 | chr2:179453412;179453411;179453410 |
| Novex-1 | 12074 | 36445;36446;36447 | chr2:178588685;178588684;178588683 | chr2:179453412;179453411;179453410 |
| Novex-2 | 12141 | 36646;36647;36648 | chr2:178588685;178588684;178588683 | chr2:179453412;179453411;179453410 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/S | rs746100195  |
-0.981 | 0.174 | N | 0.554 | 0.141 | 0.18274738541 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| N/S | rs746100195 |
-0.981 | 0.174 | N | 0.554 | 0.141 | 0.18274738541 | gnomAD-4.0.0 | 3.18532E-06 | None | None | None | None | N | None | 0 | 4.5754E-05 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.3279 | likely_benign | 0.3596 | ambiguous | -0.929 | Destabilizing | 0.218 | N | 0.555 | neutral | None | None | None | None | N |
| N/C | 0.1841 | likely_benign | 0.1713 | benign | 0.047 | Stabilizing | 0.973 | D | 0.622 | neutral | None | None | None | None | N |
| N/D | 0.5691 | likely_pathogenic | 0.5878 | pathogenic | -0.262 | Destabilizing | 0.505 | D | 0.554 | neutral | N | 0.470914712 | None | None | N |
| N/E | 0.8327 | likely_pathogenic | 0.8261 | pathogenic | -0.116 | Destabilizing | 0.575 | D | 0.563 | neutral | None | None | None | None | N |
| N/F | 0.7362 | likely_pathogenic | 0.7546 | pathogenic | -0.548 | Destabilizing | 0.906 | D | 0.643 | neutral | None | None | None | None | N |
| N/G | 0.3605 | ambiguous | 0.3833 | ambiguous | -1.306 | Destabilizing | 0.575 | D | 0.541 | neutral | None | None | None | None | N |
| N/H | 0.2305 | likely_benign | 0.2179 | benign | -0.851 | Destabilizing | 0.957 | D | 0.627 | neutral | N | 0.477119684 | None | None | N |
| N/I | 0.3391 | likely_benign | 0.3503 | ambiguous | 0.052 | Stabilizing | 0.642 | D | 0.598 | neutral | N | 0.484499517 | None | None | N |
| N/K | 0.8021 | likely_pathogenic | 0.8155 | pathogenic | -0.049 | Destabilizing | 0.505 | D | 0.569 | neutral | N | 0.468850797 | None | None | N |
| N/L | 0.306 | likely_benign | 0.3347 | benign | 0.052 | Stabilizing | 0.404 | N | 0.587 | neutral | None | None | None | None | N |
| N/M | 0.342 | ambiguous | 0.3905 | ambiguous | 0.364 | Stabilizing | 0.973 | D | 0.585 | neutral | None | None | None | None | N |
| N/P | 0.8438 | likely_pathogenic | 0.8703 | pathogenic | -0.246 | Destabilizing | 0.906 | D | 0.571 | neutral | None | None | None | None | N |
| N/Q | 0.627 | likely_pathogenic | 0.6313 | pathogenic | -0.541 | Destabilizing | 0.906 | D | 0.625 | neutral | None | None | None | None | N |
| N/R | 0.7545 | likely_pathogenic | 0.7767 | pathogenic | -0.175 | Destabilizing | 0.826 | D | 0.603 | neutral | None | None | None | None | N |
| N/S | 0.0777 | likely_benign | 0.0836 | benign | -0.83 | Destabilizing | 0.174 | N | 0.554 | neutral | N | 0.508571239 | None | None | N |
| N/T | 0.0666 | likely_benign | 0.0927 | benign | -0.472 | Destabilizing | None | N | 0.192 | neutral | N | 0.49027348 | None | None | N |
| N/V | 0.2699 | likely_benign | 0.287 | benign | -0.246 | Destabilizing | 0.404 | N | 0.587 | neutral | None | None | None | None | N |
| N/W | 0.9045 | likely_pathogenic | 0.9046 | pathogenic | -0.279 | Destabilizing | 0.991 | D | 0.653 | neutral | None | None | None | None | N |
| N/Y | 0.3954 | ambiguous | 0.3965 | ambiguous | -0.053 | Destabilizing | 0.879 | D | 0.599 | neutral | N | 0.518964378 | 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.