Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8783 | 26572;26573;26574 | chr2:178714427;178714426;178714425 | chr2:179579154;179579153;179579152 |
| N2AB | 8466 | 25621;25622;25623 | chr2:178714427;178714426;178714425 | chr2:179579154;179579153;179579152 |
| N2A | 7539 | 22840;22841;22842 | chr2:178714427;178714426;178714425 | chr2:179579154;179579153;179579152 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/K | rs1226202295  |
None | 0.001 | N | 0.623 | 0.395 | 0.774775221225 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/K | rs1226202295 |
None | 0.001 | N | 0.623 | 0.395 | 0.774775221225 | gnomAD-4.0.0 | 6.57082E-06 | None | None | None | None | N | None | 2.41231E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/L | None | None | None | D | 0.165 | 0.075 | 0.301789629655 | gnomAD-4.0.0 | 6.84237E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99501E-07 | 0 | 0 |
| I/M | rs767996372 |
-0.883 | 0.039 | N | 0.612 | 0.23 | 0.429552544315 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| I/M | rs767996372 |
-0.883 | 0.039 | N | 0.612 | 0.23 | 0.429552544315 | gnomAD-4.0.0 | 6.15819E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.19602E-06 | 0 | 1.65662E-05 |
| I/T | rs1226202295 |
-2.256 | 0.014 | N | 0.586 | 0.252 | 0.646043907412 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1226202295 |
-2.256 | 0.014 | N | 0.586 | 0.252 | 0.646043907412 | gnomAD-4.0.0 | 1.36848E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.51915E-05 | None | 0 | 0 | 8.99497E-07 | 0 | 0 |
| I/V | rs2077150875 |
None | None | N | 0.187 | 0.118 | 0.36076525451 | gnomAD-4.0.0 | 4.78966E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.598E-06 | 2.31873E-05 | 1.65673E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.241 | likely_benign | 0.2539 | benign | -2.203 | Highly Destabilizing | 0.026 | N | 0.527 | neutral | None | None | None | None | N |
| I/C | 0.5549 | ambiguous | 0.5756 | pathogenic | -1.551 | Destabilizing | 0.775 | D | 0.625 | neutral | None | None | None | None | N |
| I/D | 0.5816 | likely_pathogenic | 0.6322 | pathogenic | -1.796 | Destabilizing | 0.477 | N | 0.692 | prob.neutral | None | None | None | None | N |
| I/E | 0.4802 | ambiguous | 0.5201 | ambiguous | -1.642 | Destabilizing | 0.086 | N | 0.643 | neutral | None | None | None | None | N |
| I/F | 0.1391 | likely_benign | 0.1583 | benign | -1.359 | Destabilizing | 0.152 | N | 0.611 | neutral | None | None | None | None | N |
| I/G | 0.4964 | ambiguous | 0.5231 | ambiguous | -2.69 | Highly Destabilizing | 0.206 | N | 0.647 | neutral | None | None | None | None | N |
| I/H | 0.3949 | ambiguous | 0.4171 | ambiguous | -2.021 | Highly Destabilizing | None | N | 0.523 | neutral | None | None | None | None | N |
| I/K | 0.3093 | likely_benign | 0.3589 | ambiguous | -1.525 | Destabilizing | 0.001 | N | 0.623 | neutral | N | 0.50182571 | None | None | N |
| I/L | 0.0971 | likely_benign | 0.1035 | benign | -0.848 | Destabilizing | None | N | 0.165 | neutral | D | 0.525669425 | None | None | N |
| I/M | 0.0964 | likely_benign | 0.1042 | benign | -0.8 | Destabilizing | 0.039 | N | 0.612 | neutral | N | 0.509459032 | None | None | N |
| I/N | 0.2083 | likely_benign | 0.2253 | benign | -1.626 | Destabilizing | 0.114 | N | 0.693 | prob.neutral | None | None | None | None | N |
| I/P | 0.8384 | likely_pathogenic | 0.8743 | pathogenic | -1.274 | Destabilizing | 0.735 | D | 0.666 | neutral | None | None | None | None | N |
| I/Q | 0.3682 | ambiguous | 0.4002 | ambiguous | -1.589 | Destabilizing | 0.157 | N | 0.687 | prob.neutral | None | None | None | None | N |
| I/R | 0.2315 | likely_benign | 0.2621 | benign | -1.178 | Destabilizing | None | N | 0.445 | neutral | N | 0.484556308 | None | None | N |
| I/S | 0.2181 | likely_benign | 0.2254 | benign | -2.402 | Highly Destabilizing | 0.114 | N | 0.612 | neutral | None | None | None | None | N |
| I/T | 0.1427 | likely_benign | 0.1478 | benign | -2.104 | Highly Destabilizing | 0.014 | N | 0.586 | neutral | N | 0.493076297 | None | None | N |
| I/V | 0.073 | likely_benign | 0.0737 | benign | -1.274 | Destabilizing | None | N | 0.187 | neutral | N | 0.479723705 | None | None | N |
| I/W | 0.6663 | likely_pathogenic | 0.7291 | pathogenic | -1.604 | Destabilizing | 0.94 | D | 0.66 | neutral | None | None | None | None | N |
| I/Y | 0.3656 | ambiguous | 0.3976 | ambiguous | -1.32 | Destabilizing | 0.021 | N | 0.673 | 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.