Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18839 | 56740;56741;56742 | chr2:178599278;178599277;178599276 | chr2:179464005;179464004;179464003 |
| N2AB | 17198 | 51817;51818;51819 | chr2:178599278;178599277;178599276 | chr2:179464005;179464004;179464003 |
| N2A | 16271 | 49036;49037;49038 | chr2:178599278;178599277;178599276 | chr2:179464005;179464004;179464003 |
| N2B | 9774 | 29545;29546;29547 | chr2:178599278;178599277;178599276 | chr2:179464005;179464004;179464003 |
| Novex-1 | 9899 | 29920;29921;29922 | chr2:178599278;178599277;178599276 | chr2:179464005;179464004;179464003 |
| Novex-2 | 9966 | 30121;30122;30123 | chr2:178599278;178599277;178599276 | chr2:179464005;179464004;179464003 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | rs1368373679  |
None | 0.003 | N | 0.467 | 0.201 | 0.213573922156 | gnomAD-4.0.0 | 1.38103E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.53165E-05 | None | 0 | 0 | 0 | 1.20479E-05 | 0 |
| P/L | rs1170043972 |
-0.287 | 0.003 | N | 0.572 | 0.227 | 0.404315859256 | gnomAD-2.1.1 | 4.24E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.24E-06 | 0 |
| P/L | rs1170043972 |
-0.287 | 0.003 | N | 0.572 | 0.227 | 0.404315859256 | gnomAD-4.0.0 | 3.45487E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80674E-06 | 0 | 5.01941E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1289 | likely_benign | 0.0988 | benign | -1.767 | Destabilizing | 0.003 | N | 0.467 | neutral | N | 0.464505476 | None | None | N |
| P/C | 0.5738 | likely_pathogenic | 0.4774 | ambiguous | -1.26 | Destabilizing | 0.991 | D | 0.755 | deleterious | None | None | None | None | N |
| P/D | 0.8638 | likely_pathogenic | 0.7609 | pathogenic | -2.482 | Highly Destabilizing | 0.906 | D | 0.673 | neutral | None | None | None | None | N |
| P/E | 0.7007 | likely_pathogenic | 0.5531 | ambiguous | -2.232 | Highly Destabilizing | 0.826 | D | 0.685 | prob.neutral | None | None | None | None | N |
| P/F | 0.7985 | likely_pathogenic | 0.6982 | pathogenic | -1.015 | Destabilizing | 0.704 | D | 0.771 | deleterious | None | None | None | None | N |
| P/G | 0.5986 | likely_pathogenic | 0.46 | ambiguous | -2.319 | Highly Destabilizing | 0.404 | N | 0.702 | prob.neutral | None | None | None | None | N |
| P/H | 0.6491 | likely_pathogenic | 0.5062 | ambiguous | -2.31 | Highly Destabilizing | 0.988 | D | 0.693 | prob.neutral | N | 0.503502371 | None | None | N |
| P/I | 0.3416 | ambiguous | 0.2712 | benign | -0.216 | Destabilizing | 0.404 | N | 0.737 | prob.delet. | None | None | None | None | N |
| P/K | 0.7621 | likely_pathogenic | 0.6192 | pathogenic | -1.351 | Destabilizing | 0.826 | D | 0.684 | prob.neutral | None | None | None | None | N |
| P/L | 0.2036 | likely_benign | 0.1586 | benign | -0.216 | Destabilizing | 0.003 | N | 0.572 | neutral | N | 0.50764852 | None | None | N |
| P/M | 0.4435 | ambiguous | 0.3499 | ambiguous | -0.385 | Destabilizing | 0.826 | D | 0.704 | prob.neutral | None | None | None | None | N |
| P/N | 0.721 | likely_pathogenic | 0.5786 | pathogenic | -1.766 | Destabilizing | 0.906 | D | 0.702 | prob.neutral | None | None | None | None | N |
| P/Q | 0.5422 | ambiguous | 0.4026 | ambiguous | -1.528 | Destabilizing | 0.906 | D | 0.687 | prob.neutral | None | None | None | None | N |
| P/R | 0.676 | likely_pathogenic | 0.514 | ambiguous | -1.392 | Destabilizing | 0.879 | D | 0.705 | prob.neutral | N | 0.486911691 | None | None | N |
| P/S | 0.3813 | ambiguous | 0.2712 | benign | -2.328 | Highly Destabilizing | 0.338 | N | 0.677 | prob.neutral | N | 0.511264828 | None | None | N |
| P/T | 0.2116 | likely_benign | 0.1568 | benign | -1.931 | Destabilizing | 0.505 | D | 0.674 | neutral | N | 0.489390833 | None | None | N |
| P/V | 0.226 | likely_benign | 0.1859 | benign | -0.707 | Destabilizing | 0.018 | N | 0.541 | neutral | None | None | None | None | N |
| P/W | 0.9144 | likely_pathogenic | 0.8445 | pathogenic | -1.626 | Destabilizing | 0.991 | D | 0.717 | prob.delet. | None | None | None | None | N |
| P/Y | 0.8012 | likely_pathogenic | 0.676 | pathogenic | -1.169 | Destabilizing | 0.906 | D | 0.772 | deleterious | 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.