Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32330 | 97213;97214;97215 | chr2:178542866;178542865;178542864 | chr2:179407593;179407592;179407591 |
| N2AB | 30689 | 92290;92291;92292 | chr2:178542866;178542865;178542864 | chr2:179407593;179407592;179407591 |
| N2A | 29762 | 89509;89510;89511 | chr2:178542866;178542865;178542864 | chr2:179407593;179407592;179407591 |
| N2B | 23265 | 70018;70019;70020 | chr2:178542866;178542865;178542864 | chr2:179407593;179407592;179407591 |
| Novex-1 | 23390 | 70393;70394;70395 | chr2:178542866;178542865;178542864 | chr2:179407593;179407592;179407591 |
| Novex-2 | 23457 | 70594;70595;70596 | chr2:178542866;178542865;178542864 | chr2:179407593;179407592;179407591 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | None | None | 0.817 | N | 0.512 | 0.26 | 0.519837540645 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 0 |
| I/T | rs201023432  |
-2.365 | 0.98 | N | 0.757 | 0.605 | None | gnomAD-2.1.1 | 5.73E-05 | None | None | None | None | N | None | 0 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.18092E-04 | 0 |
| I/T | rs201023432 |
-2.365 | 0.98 | N | 0.757 | 0.605 | None | gnomAD-3.1.2 | 8.54E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.61703E-04 | 0 | 0 |
| I/T | rs201023432 |
-2.365 | 0.98 | N | 0.757 | 0.605 | None | gnomAD-4.0.0 | 2.20611E-04 | None | None | None | None | N | None | 4.00416E-05 | 1.667E-05 | None | 0 | 0 | None | 0 | 0 | 2.86492E-04 | 2.19602E-05 | 1.92117E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5224 | ambiguous | 0.4846 | ambiguous | -1.827 | Destabilizing | 0.985 | D | 0.683 | prob.neutral | None | None | None | None | N |
| I/C | 0.8306 | likely_pathogenic | 0.8201 | pathogenic | -1.157 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| I/D | 0.9899 | likely_pathogenic | 0.9905 | pathogenic | -1.379 | Destabilizing | 0.999 | D | 0.799 | deleterious | None | None | None | None | N |
| I/E | 0.9656 | likely_pathogenic | 0.9669 | pathogenic | -1.344 | Destabilizing | 0.999 | D | 0.791 | deleterious | None | None | None | None | N |
| I/F | 0.2161 | likely_benign | 0.2018 | benign | -1.189 | Destabilizing | 0.265 | N | 0.403 | neutral | N | 0.475035535 | None | None | N |
| I/G | 0.9141 | likely_pathogenic | 0.9073 | pathogenic | -2.192 | Highly Destabilizing | 0.999 | D | 0.779 | deleterious | None | None | None | None | N |
| I/H | 0.9148 | likely_pathogenic | 0.9142 | pathogenic | -1.414 | Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | N |
| I/K | 0.92 | likely_pathogenic | 0.9233 | pathogenic | -1.399 | Destabilizing | 0.999 | D | 0.794 | deleterious | None | None | None | None | N |
| I/L | 0.1507 | likely_benign | 0.1366 | benign | -0.879 | Destabilizing | 0.817 | D | 0.512 | neutral | N | 0.484404379 | None | None | N |
| I/M | 0.1272 | likely_benign | 0.1212 | benign | -0.715 | Destabilizing | 0.997 | D | 0.703 | prob.neutral | N | 0.492955074 | None | None | N |
| I/N | 0.8959 | likely_pathogenic | 0.9044 | pathogenic | -1.254 | Destabilizing | 0.999 | D | 0.791 | deleterious | N | 0.504818358 | None | None | N |
| I/P | 0.9606 | likely_pathogenic | 0.9591 | pathogenic | -1.165 | Destabilizing | 0.999 | D | 0.792 | deleterious | None | None | None | None | N |
| I/Q | 0.911 | likely_pathogenic | 0.915 | pathogenic | -1.389 | Destabilizing | 0.999 | D | 0.805 | deleterious | None | None | None | None | N |
| I/R | 0.8652 | likely_pathogenic | 0.8724 | pathogenic | -0.816 | Destabilizing | 0.999 | D | 0.789 | deleterious | None | None | None | None | N |
| I/S | 0.7175 | likely_pathogenic | 0.7021 | pathogenic | -1.874 | Destabilizing | 0.997 | D | 0.763 | deleterious | D | 0.528715304 | None | None | N |
| I/T | 0.4889 | ambiguous | 0.4691 | ambiguous | -1.72 | Destabilizing | 0.98 | D | 0.757 | deleterious | N | 0.484577738 | None | None | N |
| I/V | 0.0807 | likely_benign | 0.074 | benign | -1.165 | Destabilizing | 0.4 | N | 0.279 | neutral | N | 0.417090804 | None | None | N |
| I/W | 0.8996 | likely_pathogenic | 0.9041 | pathogenic | -1.3 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| I/Y | 0.6901 | likely_pathogenic | 0.6774 | pathogenic | -1.085 | Destabilizing | 0.991 | D | 0.774 | 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.