Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14567 | 43924;43925;43926 | chr2:178632195;178632194;178632193 | chr2:179496922;179496921;179496920 |
| N2AB | 12926 | 39001;39002;39003 | chr2:178632195;178632194;178632193 | chr2:179496922;179496921;179496920 |
| N2A | 11999 | 36220;36221;36222 | chr2:178632195;178632194;178632193 | chr2:179496922;179496921;179496920 |
| N2B | 5502 | 16729;16730;16731 | chr2:178632195;178632194;178632193 | chr2:179496922;179496921;179496920 |
| Novex-1 | 5627 | 17104;17105;17106 | chr2:178632195;178632194;178632193 | chr2:179496922;179496921;179496920 |
| Novex-2 | 5694 | 17305;17306;17307 | chr2:178632195;178632194;178632193 | chr2:179496922;179496921;179496920 |
| 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/T | rs555652524  |
-1.722 | 0.117 | N | 0.533 | 0.301 | None | gnomAD-2.1.1 | 1.25E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.76E-05 | 0 |
| R/T | rs555652524 |
-1.722 | 0.117 | N | 0.533 | 0.301 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| R/T | rs555652524 |
-1.722 | 0.117 | N | 0.533 | 0.301 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| R/T | rs555652524 |
-1.722 | 0.117 | N | 0.533 | 0.301 | None | gnomAD-4.0.0 | 1.67814E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.29317E-05 | 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 | 0.3332 | likely_benign | 0.3297 | benign | -1.772 | Destabilizing | 0.035 | N | 0.485 | neutral | None | None | None | None | N |
| R/C | 0.2717 | likely_benign | 0.2965 | benign | -1.899 | Destabilizing | 0.935 | D | 0.557 | neutral | None | None | None | None | N |
| R/D | 0.7613 | likely_pathogenic | 0.7661 | pathogenic | -0.688 | Destabilizing | 0.149 | N | 0.54 | neutral | None | None | None | None | N |
| R/E | 0.3159 | likely_benign | 0.2996 | benign | -0.535 | Destabilizing | 0.035 | N | 0.476 | neutral | None | None | None | None | N |
| R/F | 0.5553 | ambiguous | 0.5633 | ambiguous | -1.471 | Destabilizing | 0.791 | D | 0.573 | neutral | None | None | None | None | N |
| R/G | 0.2726 | likely_benign | 0.2662 | benign | -2.079 | Highly Destabilizing | 0.117 | N | 0.542 | neutral | D | 0.525468096 | None | None | N |
| R/H | 0.1556 | likely_benign | 0.1657 | benign | -1.947 | Destabilizing | 0.555 | D | 0.556 | neutral | None | None | None | None | N |
| R/I | 0.1901 | likely_benign | 0.1912 | benign | -0.913 | Destabilizing | 0.484 | N | 0.589 | neutral | N | 0.504803149 | None | None | N |
| R/K | 0.0611 | likely_benign | 0.0565 | benign | -1.585 | Destabilizing | None | N | 0.22 | neutral | N | 0.307488259 | None | None | N |
| R/L | 0.2451 | likely_benign | 0.263 | benign | -0.913 | Destabilizing | 0.149 | N | 0.542 | neutral | None | None | None | None | N |
| R/M | 0.1763 | likely_benign | 0.1849 | benign | -1.227 | Destabilizing | 0.791 | D | 0.571 | neutral | None | None | None | None | N |
| R/N | 0.5468 | ambiguous | 0.5319 | ambiguous | -1.118 | Destabilizing | 0.149 | N | 0.521 | neutral | None | None | None | None | N |
| R/P | 0.9382 | likely_pathogenic | 0.9482 | pathogenic | -1.184 | Destabilizing | 0.262 | N | 0.575 | neutral | None | None | None | None | N |
| R/Q | 0.1229 | likely_benign | 0.1232 | benign | -1.292 | Destabilizing | 0.081 | N | 0.535 | neutral | None | None | None | None | N |
| R/S | 0.3909 | ambiguous | 0.3807 | ambiguous | -2.107 | Highly Destabilizing | 0.027 | N | 0.499 | neutral | N | 0.414887216 | None | None | N |
| R/T | 0.1346 | likely_benign | 0.13 | benign | -1.764 | Destabilizing | 0.117 | N | 0.533 | neutral | N | 0.414171273 | None | None | N |
| R/V | 0.2745 | likely_benign | 0.2657 | benign | -1.184 | Destabilizing | 0.149 | N | 0.558 | neutral | None | None | None | None | N |
| R/W | 0.223 | likely_benign | 0.2472 | benign | -0.939 | Destabilizing | 0.935 | D | 0.58 | neutral | None | None | None | None | N |
| R/Y | 0.4841 | ambiguous | 0.4843 | ambiguous | -0.715 | Destabilizing | 0.555 | D | 0.58 | 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.