Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22774 | 68545;68546;68547 | chr2:178578620;178578619;178578618 | chr2:179443347;179443346;179443345 |
| N2AB | 21133 | 63622;63623;63624 | chr2:178578620;178578619;178578618 | chr2:179443347;179443346;179443345 |
| N2A | 20206 | 60841;60842;60843 | chr2:178578620;178578619;178578618 | chr2:179443347;179443346;179443345 |
| N2B | 13709 | 41350;41351;41352 | chr2:178578620;178578619;178578618 | chr2:179443347;179443346;179443345 |
| Novex-1 | 13834 | 41725;41726;41727 | chr2:178578620;178578619;178578618 | chr2:179443347;179443346;179443345 |
| Novex-2 | 13901 | 41926;41927;41928 | chr2:178578620;178578619;178578618 | chr2:179443347;179443346;179443345 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs886042240  |
-0.144 | 1.0 | N | 0.681 | 0.514 | 0.684920834152 | gnomAD-2.1.1 | 4.08E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.35E-05 | None | 0 | 0 | 0 |
| P/L | rs886042240 |
-0.144 | 1.0 | N | 0.681 | 0.514 | 0.684920834152 | gnomAD-4.0.0 | 1.59854E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.03693E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0927 | likely_benign | 0.0856 | benign | -0.526 | Destabilizing | 1.0 | D | 0.649 | neutral | N | 0.471194655 | None | None | I |
| P/C | 0.5899 | likely_pathogenic | 0.5671 | pathogenic | -0.66 | Destabilizing | 1.0 | D | 0.636 | neutral | None | None | None | None | I |
| P/D | 0.5607 | ambiguous | 0.6081 | pathogenic | -0.08 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | I |
| P/E | 0.3491 | ambiguous | 0.388 | ambiguous | -0.188 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | I |
| P/F | 0.5991 | likely_pathogenic | 0.5765 | pathogenic | -0.727 | Destabilizing | 1.0 | D | 0.578 | neutral | None | None | None | None | I |
| P/G | 0.4342 | ambiguous | 0.4182 | ambiguous | -0.667 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | I |
| P/H | 0.2717 | likely_benign | 0.2812 | benign | -0.238 | Destabilizing | 1.0 | D | 0.602 | neutral | None | None | None | None | I |
| P/I | 0.3275 | likely_benign | 0.3108 | benign | -0.305 | Destabilizing | 1.0 | D | 0.638 | neutral | None | None | None | None | I |
| P/K | 0.3664 | ambiguous | 0.41 | ambiguous | -0.353 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | I |
| P/L | 0.1487 | likely_benign | 0.1409 | benign | -0.305 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | N | 0.505316478 | None | None | I |
| P/M | 0.3205 | likely_benign | 0.2964 | benign | -0.31 | Destabilizing | 1.0 | D | 0.604 | neutral | None | None | None | None | I |
| P/N | 0.4017 | ambiguous | 0.3853 | ambiguous | -0.12 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | I |
| P/Q | 0.1808 | likely_benign | 0.1878 | benign | -0.354 | Destabilizing | 1.0 | D | 0.652 | neutral | N | 0.490135057 | None | None | I |
| P/R | 0.2616 | likely_benign | 0.2981 | benign | 0.131 | Stabilizing | 1.0 | D | 0.659 | neutral | N | 0.47674129 | None | None | I |
| P/S | 0.1712 | likely_benign | 0.1596 | benign | -0.54 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | N | 0.485184306 | None | None | I |
| P/T | 0.1398 | likely_benign | 0.1333 | benign | -0.541 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | N | 0.483298202 | None | None | I |
| P/V | 0.2093 | likely_benign | 0.1976 | benign | -0.343 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | I |
| P/W | 0.7749 | likely_pathogenic | 0.7825 | pathogenic | -0.791 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | I |
| P/Y | 0.5667 | likely_pathogenic | 0.5672 | pathogenic | -0.482 | Destabilizing | 1.0 | D | 0.587 | 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.