Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18745 | 56458;56459;56460 | chr2:178599668;178599667;178599666 | chr2:179464395;179464394;179464393 |
| N2AB | 17104 | 51535;51536;51537 | chr2:178599668;178599667;178599666 | chr2:179464395;179464394;179464393 |
| N2A | 16177 | 48754;48755;48756 | chr2:178599668;178599667;178599666 | chr2:179464395;179464394;179464393 |
| N2B | 9680 | 29263;29264;29265 | chr2:178599668;178599667;178599666 | chr2:179464395;179464394;179464393 |
| Novex-1 | 9805 | 29638;29639;29640 | chr2:178599668;178599667;178599666 | chr2:179464395;179464394;179464393 |
| Novex-2 | 9872 | 29839;29840;29841 | chr2:178599668;178599667;178599666 | chr2:179464395;179464394;179464393 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs1376102250  |
None | 0.999 | N | 0.706 | 0.337 | 0.319970858106 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.07211E-04 | 0 |
| D/N | rs1376102250 |
None | 0.999 | N | 0.706 | 0.337 | 0.319970858106 | gnomAD-4.0.0 | 1.31563E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47093E-05 | 2.07211E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2669 | likely_benign | 0.1999 | benign | -0.4 | Destabilizing | 0.998 | D | 0.655 | neutral | D | 0.527477579 | None | None | I |
| D/C | 0.6772 | likely_pathogenic | 0.6049 | pathogenic | -0.151 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | I |
| D/E | 0.2145 | likely_benign | 0.1705 | benign | -0.339 | Destabilizing | 0.619 | D | 0.317 | neutral | N | 0.463986248 | None | None | I |
| D/F | 0.7334 | likely_pathogenic | 0.6473 | pathogenic | -0.114 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | I |
| D/G | 0.1818 | likely_benign | 0.1487 | benign | -0.657 | Destabilizing | 0.996 | D | 0.658 | neutral | N | 0.45690556 | None | None | I |
| D/H | 0.3366 | likely_benign | 0.2626 | benign | -0.098 | Destabilizing | 1.0 | D | 0.675 | neutral | D | 0.531616749 | None | None | I |
| D/I | 0.6004 | likely_pathogenic | 0.4705 | ambiguous | 0.245 | Stabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | I |
| D/K | 0.3894 | ambiguous | 0.319 | benign | 0.019 | Stabilizing | 0.998 | D | 0.649 | neutral | None | None | None | None | I |
| D/L | 0.6076 | likely_pathogenic | 0.5075 | ambiguous | 0.245 | Stabilizing | 0.999 | D | 0.685 | prob.neutral | None | None | None | None | I |
| D/M | 0.7218 | likely_pathogenic | 0.6102 | pathogenic | 0.401 | Stabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | I |
| D/N | 0.0911 | likely_benign | 0.0737 | benign | -0.368 | Destabilizing | 0.999 | D | 0.706 | prob.neutral | N | 0.465775759 | None | None | I |
| D/P | 0.8652 | likely_pathogenic | 0.814 | pathogenic | 0.053 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| D/Q | 0.3883 | ambiguous | 0.3082 | benign | -0.278 | Destabilizing | 0.998 | D | 0.736 | prob.delet. | None | None | None | None | I |
| D/R | 0.444 | ambiguous | 0.3706 | ambiguous | 0.241 | Stabilizing | 0.998 | D | 0.689 | prob.neutral | None | None | None | None | I |
| D/S | 0.1414 | likely_benign | 0.1108 | benign | -0.507 | Destabilizing | 0.994 | D | 0.675 | prob.neutral | None | None | None | None | I |
| D/T | 0.2823 | likely_benign | 0.2049 | benign | -0.301 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | None | None | None | None | I |
| D/V | 0.4362 | ambiguous | 0.3291 | benign | 0.053 | Stabilizing | 0.999 | D | 0.691 | prob.neutral | N | 0.488214452 | None | None | I |
| D/W | 0.9255 | likely_pathogenic | 0.9031 | pathogenic | 0.071 | Stabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | I |
| D/Y | 0.3091 | likely_benign | 0.2583 | benign | 0.122 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | N | 0.493240881 | None | None | I |
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.