Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16032 | 48319;48320;48321 | chr2:178616795;178616794;178616793 | chr2:179481522;179481521;179481520 |
| N2AB | 14391 | 43396;43397;43398 | chr2:178616795;178616794;178616793 | chr2:179481522;179481521;179481520 |
| N2A | 13464 | 40615;40616;40617 | chr2:178616795;178616794;178616793 | chr2:179481522;179481521;179481520 |
| N2B | 6967 | 21124;21125;21126 | chr2:178616795;178616794;178616793 | chr2:179481522;179481521;179481520 |
| Novex-1 | 7092 | 21499;21500;21501 | chr2:178616795;178616794;178616793 | chr2:179481522;179481521;179481520 |
| Novex-2 | 7159 | 21700;21701;21702 | chr2:178616795;178616794;178616793 | chr2:179481522;179481521;179481520 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs879171203  |
-1.714 | 0.122 | N | 0.293 | 0.207 | None | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| I/T | rs879171203 |
-1.714 | 0.122 | N | 0.293 | 0.207 | None | gnomAD-4.0.0 | 1.59322E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8621E-06 | 0 | 0 |
| I/V | rs794729443 |
-0.969 | 0.816 | N | 0.351 | 0.118 | 0.532216101619 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| I/V | rs794729443 |
-0.969 | 0.816 | N | 0.351 | 0.118 | 0.532216101619 | gnomAD-4.0.0 | 1.59324E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86211E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3488 | ambiguous | 0.3542 | ambiguous | -1.554 | Destabilizing | 0.931 | D | 0.584 | neutral | None | None | None | None | N |
| I/C | 0.56 | ambiguous | 0.5598 | ambiguous | -0.878 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| I/D | 0.6722 | likely_pathogenic | 0.68 | pathogenic | -0.41 | Destabilizing | 0.996 | D | 0.755 | deleterious | None | None | None | None | N |
| I/E | 0.516 | ambiguous | 0.5219 | ambiguous | -0.311 | Destabilizing | 0.996 | D | 0.741 | deleterious | None | None | None | None | N |
| I/F | 0.2293 | likely_benign | 0.2118 | benign | -0.858 | Destabilizing | 0.998 | D | 0.627 | neutral | D | 0.550525758 | None | None | N |
| I/G | 0.6687 | likely_pathogenic | 0.6365 | pathogenic | -1.96 | Destabilizing | 0.996 | D | 0.723 | prob.delet. | None | None | None | None | N |
| I/H | 0.3782 | ambiguous | 0.3782 | ambiguous | -1.137 | Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | N |
| I/K | 0.189 | likely_benign | 0.1932 | benign | -0.713 | Destabilizing | 0.991 | D | 0.752 | deleterious | None | None | None | None | N |
| I/L | 0.1547 | likely_benign | 0.1519 | benign | -0.473 | Destabilizing | 0.91 | D | 0.39 | neutral | N | 0.486791951 | None | None | N |
| I/M | 0.1377 | likely_benign | 0.1334 | benign | -0.472 | Destabilizing | 0.998 | D | 0.622 | neutral | D | 0.550087358 | None | None | N |
| I/N | 0.1812 | likely_benign | 0.201 | benign | -0.681 | Destabilizing | 0.994 | D | 0.762 | deleterious | N | 0.502866067 | None | None | N |
| I/P | 0.672 | likely_pathogenic | 0.6897 | pathogenic | -0.804 | Destabilizing | 0.999 | D | 0.772 | deleterious | None | None | None | None | N |
| I/Q | 0.34 | likely_benign | 0.3416 | ambiguous | -0.685 | Destabilizing | 0.999 | D | 0.772 | deleterious | None | None | None | None | N |
| I/R | 0.1636 | likely_benign | 0.1669 | benign | -0.398 | Destabilizing | 0.996 | D | 0.777 | deleterious | None | None | None | None | N |
| I/S | 0.2548 | likely_benign | 0.2732 | benign | -1.48 | Destabilizing | 0.925 | D | 0.65 | neutral | N | 0.506882648 | None | None | N |
| I/T | 0.1769 | likely_benign | 0.1767 | benign | -1.243 | Destabilizing | 0.122 | N | 0.293 | neutral | N | 0.442253551 | None | None | N |
| I/V | 0.093 | likely_benign | 0.086 | benign | -0.804 | Destabilizing | 0.816 | D | 0.351 | neutral | N | 0.504974046 | None | None | N |
| I/W | 0.8134 | likely_pathogenic | 0.7613 | pathogenic | -0.978 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | N |
| I/Y | 0.4666 | ambiguous | 0.479 | ambiguous | -0.692 | Destabilizing | 0.999 | D | 0.723 | 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.