Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14103 | 42532;42533;42534 | chr2:178634474;178634473;178634472 | chr2:179499201;179499200;179499199 |
| N2AB | 12462 | 37609;37610;37611 | chr2:178634474;178634473;178634472 | chr2:179499201;179499200;179499199 |
| N2A | 11535 | 34828;34829;34830 | chr2:178634474;178634473;178634472 | chr2:179499201;179499200;179499199 |
| N2B | 5038 | 15337;15338;15339 | chr2:178634474;178634473;178634472 | chr2:179499201;179499200;179499199 |
| Novex-1 | 5163 | 15712;15713;15714 | chr2:178634474;178634473;178634472 | chr2:179499201;179499200;179499199 |
| Novex-2 | 5230 | 15913;15914;15915 | chr2:178634474;178634473;178634472 | chr2:179499201;179499200;179499199 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | None | None | 1.0 | D | 0.604 | 0.419 | 0.492200611407 | gnomAD-4.0.0 | 1.59233E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86017E-06 | 0 | 0 |
| D/V | rs775487599  |
0.298 | 1.0 | D | 0.746 | 0.57 | 0.724769792947 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| D/V | rs775487599 |
0.298 | 1.0 | D | 0.746 | 0.57 | 0.724769792947 | gnomAD-4.0.0 | 3.18463E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72027E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.6648 | likely_pathogenic | 0.5076 | ambiguous | -0.206 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | D | 0.633816085 | None | None | N |
| D/C | 0.9766 | likely_pathogenic | 0.9467 | pathogenic | -0.102 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/E | 0.5468 | ambiguous | 0.4388 | ambiguous | -0.278 | Destabilizing | 1.0 | D | 0.418 | neutral | N | 0.50529689 | None | None | N |
| D/F | 0.9462 | likely_pathogenic | 0.9141 | pathogenic | -0.12 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| D/G | 0.7224 | likely_pathogenic | 0.581 | pathogenic | -0.408 | Destabilizing | 1.0 | D | 0.646 | neutral | D | 0.601977915 | None | None | N |
| D/H | 0.8746 | likely_pathogenic | 0.7458 | pathogenic | 0.115 | Stabilizing | 1.0 | D | 0.647 | neutral | D | 0.665281409 | None | None | N |
| D/I | 0.8929 | likely_pathogenic | 0.8109 | pathogenic | 0.279 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| D/K | 0.9084 | likely_pathogenic | 0.8005 | pathogenic | 0.125 | Stabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | N |
| D/L | 0.8845 | likely_pathogenic | 0.8077 | pathogenic | 0.279 | Stabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| D/M | 0.9556 | likely_pathogenic | 0.9241 | pathogenic | 0.28 | Stabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| D/N | 0.4219 | ambiguous | 0.241 | benign | -0.099 | Destabilizing | 1.0 | D | 0.604 | neutral | D | 0.581100412 | None | None | N |
| D/P | 0.9866 | likely_pathogenic | 0.9791 | pathogenic | 0.14 | Stabilizing | 1.0 | D | 0.672 | neutral | None | None | None | None | N |
| D/Q | 0.8713 | likely_pathogenic | 0.7605 | pathogenic | -0.054 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| D/R | 0.9067 | likely_pathogenic | 0.8069 | pathogenic | 0.381 | Stabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| D/S | 0.5239 | ambiguous | 0.3317 | benign | -0.241 | Destabilizing | 1.0 | D | 0.618 | neutral | None | None | None | None | N |
| D/T | 0.7874 | likely_pathogenic | 0.636 | pathogenic | -0.088 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| D/V | 0.7418 | likely_pathogenic | 0.6042 | pathogenic | 0.14 | Stabilizing | 1.0 | D | 0.746 | deleterious | D | 0.663070497 | None | None | N |
| D/W | 0.9877 | likely_pathogenic | 0.9793 | pathogenic | -0.017 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/Y | 0.768 | likely_pathogenic | 0.6173 | pathogenic | 0.102 | Stabilizing | 1.0 | D | 0.704 | prob.neutral | D | 0.725757853 | 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.