Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33145 | 99658;99659;99660 | chr2:178537774;178537773;178537772 | chr2:179402501;179402500;179402499 |
| N2AB | 31504 | 94735;94736;94737 | chr2:178537774;178537773;178537772 | chr2:179402501;179402500;179402499 |
| N2A | 30577 | 91954;91955;91956 | chr2:178537774;178537773;178537772 | chr2:179402501;179402500;179402499 |
| N2B | 24080 | 72463;72464;72465 | chr2:178537774;178537773;178537772 | chr2:179402501;179402500;179402499 |
| Novex-1 | 24205 | 72838;72839;72840 | chr2:178537774;178537773;178537772 | chr2:179402501;179402500;179402499 |
| Novex-2 | 24272 | 73039;73040;73041 | chr2:178537774;178537773;178537772 | chr2:179402501;179402500;179402499 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs371531675  |
0.128 | 1.0 | N | 0.72 | 0.208 | None | gnomAD-2.1.1 | 4.28E-05 | None | None | None | None | N | None | 2.48118E-04 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 3.12E-05 | 1.4041E-04 |
| R/Q | rs371531675 |
0.128 | 1.0 | N | 0.72 | 0.208 | None | gnomAD-3.1.2 | 6.58E-05 | None | None | None | None | N | None | 7.24E-05 | 3.93443E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs371531675 |
0.128 | 1.0 | N | 0.72 | 0.208 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs371531675 |
0.128 | 1.0 | N | 0.72 | 0.208 | None | gnomAD-4.0.0 | 4.58588E-05 | None | None | None | None | N | None | 8.00107E-05 | 1.16717E-04 | None | 0 | 2.22876E-05 | None | 0 | 0 | 4.32304E-05 | 1.09815E-05 | 1.28053E-04 |
| R/W | rs1338284042 |
-0.461 | 1.0 | N | 0.757 | 0.299 | 0.258283824007 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/W | rs1338284042 |
-0.461 | 1.0 | N | 0.757 | 0.299 | 0.258283824007 | gnomAD-4.0.0 | 5.47384E-06 | None | None | None | None | N | None | 0 | 4.47387E-05 | None | 0 | 5.0388E-05 | None | 0 | 0 | 3.59794E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7476 | likely_pathogenic | 0.8225 | pathogenic | -0.14 | Destabilizing | 0.998 | D | 0.579 | neutral | None | None | None | None | N |
| R/C | 0.4705 | ambiguous | 0.5923 | pathogenic | -0.465 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| R/D | 0.889 | likely_pathogenic | 0.9096 | pathogenic | -0.438 | Destabilizing | 0.999 | D | 0.647 | neutral | None | None | None | None | N |
| R/E | 0.7117 | likely_pathogenic | 0.7635 | pathogenic | -0.424 | Destabilizing | 0.994 | D | 0.649 | neutral | None | None | None | None | N |
| R/F | 0.9003 | likely_pathogenic | 0.9239 | pathogenic | -0.525 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| R/G | 0.5187 | ambiguous | 0.6359 | pathogenic | -0.217 | Destabilizing | 1.0 | D | 0.576 | neutral | N | 0.410876042 | None | None | N |
| R/H | 0.2333 | likely_benign | 0.3071 | benign | -0.679 | Destabilizing | 0.999 | D | 0.764 | deleterious | None | None | None | None | N |
| R/I | 0.7222 | likely_pathogenic | 0.7943 | pathogenic | 0.017 | Stabilizing | 0.999 | D | 0.725 | prob.delet. | None | None | None | None | N |
| R/K | 0.2008 | likely_benign | 0.2268 | benign | -0.444 | Destabilizing | 0.964 | D | 0.554 | neutral | None | None | None | None | N |
| R/L | 0.6315 | likely_pathogenic | 0.7119 | pathogenic | 0.017 | Stabilizing | 0.999 | D | 0.576 | neutral | N | 0.47298608 | None | None | N |
| R/M | 0.7154 | likely_pathogenic | 0.7888 | pathogenic | -0.302 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| R/N | 0.8254 | likely_pathogenic | 0.868 | pathogenic | -0.382 | Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | N |
| R/P | 0.7157 | likely_pathogenic | 0.8007 | pathogenic | -0.022 | Destabilizing | 1.0 | D | 0.659 | neutral | N | 0.416399292 | None | None | N |
| R/Q | 0.1896 | likely_benign | 0.2583 | benign | -0.382 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | N | 0.456669834 | None | None | N |
| R/S | 0.7763 | likely_pathogenic | 0.8515 | pathogenic | -0.493 | Destabilizing | 0.999 | D | 0.624 | neutral | None | None | None | None | N |
| R/T | 0.6674 | likely_pathogenic | 0.7605 | pathogenic | -0.405 | Destabilizing | 0.999 | D | 0.627 | neutral | None | None | None | None | N |
| R/V | 0.7705 | likely_pathogenic | 0.84 | pathogenic | -0.022 | Destabilizing | 0.998 | D | 0.693 | prob.neutral | None | None | None | None | N |
| R/W | 0.4583 | ambiguous | 0.5549 | ambiguous | -0.765 | Destabilizing | 1.0 | D | 0.757 | deleterious | N | 0.513563267 | None | None | N |
| R/Y | 0.7552 | likely_pathogenic | 0.8115 | pathogenic | -0.407 | Destabilizing | 0.999 | D | 0.686 | prob.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.