Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13727 | 41404;41405;41406 | chr2:178636548;178636547;178636546 | chr2:179501275;179501274;179501273 |
| N2AB | 12086 | 36481;36482;36483 | chr2:178636548;178636547;178636546 | chr2:179501275;179501274;179501273 |
| N2A | 11159 | 33700;33701;33702 | chr2:178636548;178636547;178636546 | chr2:179501275;179501274;179501273 |
| N2B | 4662 | 14209;14210;14211 | chr2:178636548;178636547;178636546 | chr2:179501275;179501274;179501273 |
| Novex-1 | 4787 | 14584;14585;14586 | chr2:178636548;178636547;178636546 | chr2:179501275;179501274;179501273 |
| Novex-2 | 4854 | 14785;14786;14787 | chr2:178636548;178636547;178636546 | chr2:179501275;179501274;179501273 |
| 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/C | rs397517563  |
-0.017 | 1.0 | D | 0.702 | 0.508 | 0.721734935014 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/C | rs397517563 |
-0.017 | 1.0 | D | 0.702 | 0.508 | 0.721734935014 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 1.93949E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/C | rs397517563 |
-0.017 | 1.0 | D | 0.702 | 0.508 | 0.721734935014 | gnomAD-4.0.0 | 5.12692E-06 | None | None | None | None | N | None | 1.69205E-05 | 0 | None | 0 | 2.43002E-05 | None | 0 | 0 | 2.39419E-06 | 1.3402E-05 | 0 |
| R/H | rs750520224 |
-0.773 | 1.0 | N | 0.729 | 0.452 | 0.416328079214 | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | N | None | 0 | 1.15955E-04 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 1.65948E-04 |
| R/H | rs750520224 |
-0.773 | 1.0 | N | 0.729 | 0.452 | 0.416328079214 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs750520224 |
-0.773 | 1.0 | N | 0.729 | 0.452 | 0.416328079214 | gnomAD-4.0.0 | 1.4876E-05 | None | None | None | None | N | None | 0 | 8.33945E-05 | None | 0 | 0 | None | 0 | 0 | 1.27164E-05 | 0 | 6.40677E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8149 | likely_pathogenic | 0.9402 | pathogenic | 0.094 | Stabilizing | 0.999 | D | 0.629 | neutral | None | None | None | None | N |
| R/C | 0.6863 | likely_pathogenic | 0.8411 | pathogenic | -0.216 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | D | 0.649186938 | None | None | N |
| R/D | 0.9484 | likely_pathogenic | 0.983 | pathogenic | -0.3 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| R/E | 0.7944 | likely_pathogenic | 0.9058 | pathogenic | -0.259 | Destabilizing | 0.999 | D | 0.664 | neutral | None | None | None | None | N |
| R/F | 0.9117 | likely_pathogenic | 0.9639 | pathogenic | -0.244 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| R/G | 0.7208 | likely_pathogenic | 0.8914 | pathogenic | -0.04 | Destabilizing | 1.0 | D | 0.629 | neutral | N | 0.510603052 | None | None | N |
| R/H | 0.3184 | likely_benign | 0.5227 | ambiguous | -0.59 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | N | 0.513236722 | None | None | N |
| R/I | 0.7508 | likely_pathogenic | 0.8768 | pathogenic | 0.399 | Stabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| R/K | 0.2478 | likely_benign | 0.3601 | ambiguous | -0.118 | Destabilizing | 0.998 | D | 0.534 | neutral | None | None | None | None | N |
| R/L | 0.6607 | likely_pathogenic | 0.8239 | pathogenic | 0.399 | Stabilizing | 1.0 | D | 0.629 | neutral | N | 0.510603052 | None | None | N |
| R/M | 0.7577 | likely_pathogenic | 0.8962 | pathogenic | -0.078 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | None | None | None | None | N |
| R/N | 0.9197 | likely_pathogenic | 0.9738 | pathogenic | -0.06 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| R/P | 0.8293 | likely_pathogenic | 0.9325 | pathogenic | 0.315 | Stabilizing | 1.0 | D | 0.68 | prob.neutral | N | 0.492201796 | None | None | N |
| R/Q | 0.2646 | likely_benign | 0.4471 | ambiguous | -0.072 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| R/S | 0.8752 | likely_pathogenic | 0.9601 | pathogenic | -0.197 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | N | 0.493222884 | None | None | N |
| R/T | 0.7007 | likely_pathogenic | 0.8948 | pathogenic | -0.052 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | N |
| R/V | 0.7813 | likely_pathogenic | 0.9077 | pathogenic | 0.315 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| R/W | 0.5554 | ambiguous | 0.7376 | pathogenic | -0.461 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| R/Y | 0.8308 | likely_pathogenic | 0.9305 | pathogenic | -0.047 | Destabilizing | 1.0 | D | 0.689 | 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.