Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25165 | 75718;75719;75720 | chr2:178570639;178570638;178570637 | chr2:179435366;179435365;179435364 |
| N2AB | 23524 | 70795;70796;70797 | chr2:178570639;178570638;178570637 | chr2:179435366;179435365;179435364 |
| N2A | 22597 | 68014;68015;68016 | chr2:178570639;178570638;178570637 | chr2:179435366;179435365;179435364 |
| N2B | 16100 | 48523;48524;48525 | chr2:178570639;178570638;178570637 | chr2:179435366;179435365;179435364 |
| Novex-1 | 16225 | 48898;48899;48900 | chr2:178570639;178570638;178570637 | chr2:179435366;179435365;179435364 |
| Novex-2 | 16292 | 49099;49100;49101 | chr2:178570639;178570638;178570637 | chr2:179435366;179435365;179435364 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs879163890  |
-0.366 | 0.025 | N | 0.295 | 0.228 | 0.261217442401 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 1.24028E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| F/L | rs879163890 |
-0.366 | 0.025 | N | 0.295 | 0.228 | 0.261217442401 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| F/L | rs879163890 |
-0.366 | 0.025 | N | 0.295 | 0.228 | 0.261217442401 | gnomAD-4.0.0 | 3.84489E-06 | None | None | None | None | N | None | 5.07786E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.3328 | likely_benign | 0.3771 | ambiguous | -1.371 | Destabilizing | 0.916 | D | 0.648 | neutral | None | None | None | None | N |
| F/C | 0.2619 | likely_benign | 0.3023 | benign | -0.61 | Destabilizing | 0.999 | D | 0.698 | prob.neutral | N | 0.493187975 | None | None | N |
| F/D | 0.5493 | ambiguous | 0.6058 | pathogenic | 0.26 | Stabilizing | 0.996 | D | 0.715 | prob.delet. | None | None | None | None | N |
| F/E | 0.6688 | likely_pathogenic | 0.7152 | pathogenic | 0.286 | Stabilizing | 0.987 | D | 0.717 | prob.delet. | None | None | None | None | N |
| F/G | 0.5806 | likely_pathogenic | 0.6485 | pathogenic | -1.615 | Destabilizing | 0.987 | D | 0.713 | prob.delet. | None | None | None | None | N |
| F/H | 0.4161 | ambiguous | 0.466 | ambiguous | 0.054 | Stabilizing | 0.999 | D | 0.642 | neutral | None | None | None | None | N |
| F/I | 0.1616 | likely_benign | 0.1821 | benign | -0.696 | Destabilizing | 0.805 | D | 0.605 | neutral | N | 0.471797655 | None | None | N |
| F/K | 0.6109 | likely_pathogenic | 0.6952 | pathogenic | -0.495 | Destabilizing | 0.987 | D | 0.715 | prob.delet. | None | None | None | None | N |
| F/L | 0.7166 | likely_pathogenic | 0.7687 | pathogenic | -0.696 | Destabilizing | 0.025 | N | 0.295 | neutral | N | 0.505563512 | None | None | N |
| F/M | 0.3417 | ambiguous | 0.388 | ambiguous | -0.619 | Destabilizing | 0.975 | D | 0.658 | neutral | None | None | None | None | N |
| F/N | 0.3811 | ambiguous | 0.4037 | ambiguous | -0.557 | Destabilizing | 0.996 | D | 0.713 | prob.delet. | None | None | None | None | N |
| F/P | 0.9586 | likely_pathogenic | 0.9764 | pathogenic | -0.907 | Destabilizing | 0.996 | D | 0.71 | prob.delet. | None | None | None | None | N |
| F/Q | 0.6066 | likely_pathogenic | 0.6569 | pathogenic | -0.586 | Destabilizing | 0.996 | D | 0.709 | prob.delet. | None | None | None | None | N |
| F/R | 0.5231 | ambiguous | 0.6028 | pathogenic | 0.032 | Stabilizing | 0.987 | D | 0.716 | prob.delet. | None | None | None | None | N |
| F/S | 0.231 | likely_benign | 0.2591 | benign | -1.264 | Destabilizing | 0.983 | D | 0.689 | prob.neutral | N | 0.438010368 | None | None | N |
| F/T | 0.2126 | likely_benign | 0.2456 | benign | -1.142 | Destabilizing | 0.975 | D | 0.657 | neutral | None | None | None | None | N |
| F/V | 0.1627 | likely_benign | 0.1807 | benign | -0.907 | Destabilizing | 0.805 | D | 0.629 | neutral | N | 0.486535034 | None | None | N |
| F/W | 0.4623 | ambiguous | 0.5417 | ambiguous | -0.212 | Destabilizing | 0.999 | D | 0.641 | neutral | None | None | None | None | N |
| F/Y | 0.1327 | likely_benign | 0.1436 | benign | -0.335 | Destabilizing | 0.944 | D | 0.569 | neutral | N | 0.432836622 | 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.