Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23846 | 71761;71762;71763 | chr2:178574596;178574595;178574594 | chr2:179439323;179439322;179439321 |
| N2AB | 22205 | 66838;66839;66840 | chr2:178574596;178574595;178574594 | chr2:179439323;179439322;179439321 |
| N2A | 21278 | 64057;64058;64059 | chr2:178574596;178574595;178574594 | chr2:179439323;179439322;179439321 |
| N2B | 14781 | 44566;44567;44568 | chr2:178574596;178574595;178574594 | chr2:179439323;179439322;179439321 |
| Novex-1 | 14906 | 44941;44942;44943 | chr2:178574596;178574595;178574594 | chr2:179439323;179439322;179439321 |
| Novex-2 | 14973 | 45142;45143;45144 | chr2:178574596;178574595;178574594 | chr2:179439323;179439322;179439321 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | rs763759336  |
-1.167 | 0.896 | N | 0.455 | 0.191 | 0.285698343383 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| S/G | rs763759336 |
-1.167 | 0.896 | N | 0.455 | 0.191 | 0.285698343383 | gnomAD-4.0.0 | 2.73745E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59842E-06 | 0 | 0 |
| S/N | rs760506346 |
-0.955 | 0.896 | D | 0.526 | 0.231 | 0.298056030225 | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.7983E-04 | None | 6.55E-05 | None | 0 | 0 | 0 |
| S/N | rs760506346 |
-0.955 | 0.896 | D | 0.526 | 0.231 | 0.298056030225 | gnomAD-4.0.0 | 1.43723E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.26167E-04 | None | 0 | 1.73671E-04 | 5.39786E-06 | 1.04394E-04 | 0 |
| S/R | rs763759336 |
None | 0.938 | N | 0.626 | 0.25 | 0.337868961071 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06954E-04 | 0 |
| S/R | rs763759336 |
None | 0.938 | N | 0.626 | 0.25 | 0.337868961071 | gnomAD-4.0.0 | 6.57341E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.06954E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0716 | likely_benign | 0.0728 | benign | -0.578 | Destabilizing | 0.825 | D | 0.459 | neutral | None | None | None | None | N |
| S/C | 0.0818 | likely_benign | 0.0791 | benign | -0.346 | Destabilizing | 0.999 | D | 0.694 | prob.neutral | N | 0.483025622 | None | None | N |
| S/D | 0.451 | ambiguous | 0.4487 | ambiguous | -0.924 | Destabilizing | 0.919 | D | 0.501 | neutral | None | None | None | None | N |
| S/E | 0.4348 | ambiguous | 0.4644 | ambiguous | -0.805 | Destabilizing | 0.851 | D | 0.475 | neutral | None | None | None | None | N |
| S/F | 0.1476 | likely_benign | 0.1443 | benign | -0.392 | Destabilizing | 0.996 | D | 0.739 | prob.delet. | None | None | None | None | N |
| S/G | 0.0842 | likely_benign | 0.0819 | benign | -0.945 | Destabilizing | 0.896 | D | 0.455 | neutral | N | 0.478293979 | None | None | N |
| S/H | 0.2403 | likely_benign | 0.2548 | benign | -1.444 | Destabilizing | 0.997 | D | 0.697 | prob.neutral | None | None | None | None | N |
| S/I | 0.1187 | likely_benign | 0.1147 | benign | 0.328 | Stabilizing | 0.968 | D | 0.688 | prob.neutral | N | 0.485240894 | None | None | N |
| S/K | 0.4873 | ambiguous | 0.5252 | ambiguous | -0.531 | Destabilizing | 0.851 | D | 0.461 | neutral | None | None | None | None | N |
| S/L | 0.0785 | likely_benign | 0.0812 | benign | 0.328 | Stabilizing | 0.919 | D | 0.585 | neutral | None | None | None | None | N |
| S/M | 0.1495 | likely_benign | 0.1543 | benign | 0.358 | Stabilizing | 0.997 | D | 0.697 | prob.neutral | None | None | None | None | N |
| S/N | 0.1288 | likely_benign | 0.1288 | benign | -0.885 | Destabilizing | 0.896 | D | 0.526 | neutral | D | 0.526719857 | None | None | N |
| S/P | 0.9091 | likely_pathogenic | 0.9011 | pathogenic | 0.063 | Stabilizing | 0.988 | D | 0.633 | neutral | None | None | None | None | N |
| S/Q | 0.3261 | likely_benign | 0.3572 | ambiguous | -0.752 | Destabilizing | 0.261 | N | 0.382 | neutral | None | None | None | None | N |
| S/R | 0.3744 | ambiguous | 0.3866 | ambiguous | -0.762 | Destabilizing | 0.938 | D | 0.626 | neutral | N | 0.457070558 | None | None | N |
| S/T | 0.0666 | likely_benign | 0.0653 | benign | -0.643 | Destabilizing | 0.046 | N | 0.265 | neutral | N | 0.422341908 | None | None | N |
| S/V | 0.1361 | likely_benign | 0.1358 | benign | 0.063 | Stabilizing | 0.919 | D | 0.595 | neutral | None | None | None | None | N |
| S/W | 0.3314 | likely_benign | 0.3096 | benign | -0.617 | Destabilizing | 0.999 | D | 0.779 | deleterious | None | None | None | None | N |
| S/Y | 0.1614 | likely_benign | 0.154 | benign | -0.228 | Destabilizing | 0.996 | D | 0.738 | prob.delet. | 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.