Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15703 | 47332;47333;47334 | chr2:178618351;178618350;178618349 | chr2:179483078;179483077;179483076 |
| N2AB | 14062 | 42409;42410;42411 | chr2:178618351;178618350;178618349 | chr2:179483078;179483077;179483076 |
| N2A | 13135 | 39628;39629;39630 | chr2:178618351;178618350;178618349 | chr2:179483078;179483077;179483076 |
| N2B | 6638 | 20137;20138;20139 | chr2:178618351;178618350;178618349 | chr2:179483078;179483077;179483076 |
| Novex-1 | 6763 | 20512;20513;20514 | chr2:178618351;178618350;178618349 | chr2:179483078;179483077;179483076 |
| Novex-2 | 6830 | 20713;20714;20715 | chr2:178618351;178618350;178618349 | chr2:179483078;179483077;179483076 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs949814758  |
-0.086 | 1.0 | N | 0.583 | 0.425 | 0.444807159249 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.62E-05 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/I | rs949814758 |
-0.086 | 1.0 | N | 0.583 | 0.425 | 0.444807159249 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| T/I | rs949814758 |
-0.086 | 1.0 | N | 0.583 | 0.425 | 0.444807159249 | gnomAD-4.0.0 | 9.30269E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.64636E-04 | 8.48094E-07 | 1.20799E-04 | 3.20554E-05 |
| T/P | None | None | 1.0 | N | 0.581 | 0.542 | 0.392702134506 | gnomAD-4.0.0 | 1.59362E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86259E-06 | 0 | 0 |
| T/S | rs780903648 |
-0.49 | 0.999 | N | 0.527 | 0.325 | 0.268211541103 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| T/S | rs780903648 |
-0.49 | 0.999 | N | 0.527 | 0.325 | 0.268211541103 | gnomAD-4.0.0 | 6.84645E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99897E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1848 | likely_benign | 0.144 | benign | -0.437 | Destabilizing | 0.999 | D | 0.513 | neutral | N | 0.453762865 | None | None | I |
| T/C | 0.8473 | likely_pathogenic | 0.6829 | pathogenic | -0.388 | Destabilizing | 1.0 | D | 0.619 | neutral | None | None | None | None | I |
| T/D | 0.792 | likely_pathogenic | 0.6886 | pathogenic | 0.268 | Stabilizing | 1.0 | D | 0.608 | neutral | None | None | None | None | I |
| T/E | 0.7344 | likely_pathogenic | 0.6286 | pathogenic | 0.234 | Stabilizing | 1.0 | D | 0.613 | neutral | None | None | None | None | I |
| T/F | 0.6826 | likely_pathogenic | 0.5373 | ambiguous | -0.708 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | I |
| T/G | 0.3656 | ambiguous | 0.2951 | benign | -0.621 | Destabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | I |
| T/H | 0.647 | likely_pathogenic | 0.516 | ambiguous | -0.741 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | I |
| T/I | 0.5353 | ambiguous | 0.416 | ambiguous | -0.058 | Destabilizing | 1.0 | D | 0.583 | neutral | N | 0.514301005 | None | None | I |
| T/K | 0.6238 | likely_pathogenic | 0.5262 | ambiguous | -0.446 | Destabilizing | 1.0 | D | 0.614 | neutral | None | None | None | None | I |
| T/L | 0.2859 | likely_benign | 0.2222 | benign | -0.058 | Destabilizing | 0.999 | D | 0.551 | neutral | None | None | None | None | I |
| T/M | 0.2164 | likely_benign | 0.1746 | benign | -0.142 | Destabilizing | 1.0 | D | 0.621 | neutral | None | None | None | None | I |
| T/N | 0.2247 | likely_benign | 0.1686 | benign | -0.278 | Destabilizing | 1.0 | D | 0.587 | neutral | N | 0.479431931 | None | None | I |
| T/P | 0.4681 | ambiguous | 0.431 | ambiguous | -0.154 | Destabilizing | 1.0 | D | 0.581 | neutral | N | 0.471199533 | None | None | I |
| T/Q | 0.499 | ambiguous | 0.4048 | ambiguous | -0.415 | Destabilizing | 1.0 | D | 0.606 | neutral | None | None | None | None | I |
| T/R | 0.6082 | likely_pathogenic | 0.5388 | ambiguous | -0.175 | Destabilizing | 1.0 | D | 0.59 | neutral | None | None | None | None | I |
| T/S | 0.2157 | likely_benign | 0.1723 | benign | -0.532 | Destabilizing | 0.999 | D | 0.527 | neutral | N | 0.461528128 | None | None | I |
| T/V | 0.3715 | ambiguous | 0.2753 | benign | -0.154 | Destabilizing | 0.999 | D | 0.54 | neutral | None | None | None | None | I |
| T/W | 0.9211 | likely_pathogenic | 0.8617 | pathogenic | -0.724 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| T/Y | 0.6889 | likely_pathogenic | 0.532 | ambiguous | -0.452 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | I |
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.