Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14257 | 42994;42995;42996 | chr2:178633590;178633589;178633588 | chr2:179498317;179498316;179498315 |
| N2AB | 12616 | 38071;38072;38073 | chr2:178633590;178633589;178633588 | chr2:179498317;179498316;179498315 |
| N2A | 11689 | 35290;35291;35292 | chr2:178633590;178633589;178633588 | chr2:179498317;179498316;179498315 |
| N2B | 5192 | 15799;15800;15801 | chr2:178633590;178633589;178633588 | chr2:179498317;179498316;179498315 |
| Novex-1 | 5317 | 16174;16175;16176 | chr2:178633590;178633589;178633588 | chr2:179498317;179498316;179498315 |
| Novex-2 | 5384 | 16375;16376;16377 | chr2:178633590;178633589;178633588 | chr2:179498317;179498316;179498315 |
| 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 | rs746571349  |
-0.343 | 1.0 | N | 0.723 | 0.426 | 0.43912465853 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs746571349 |
-0.343 | 1.0 | N | 0.723 | 0.426 | 0.43912465853 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs746571349 |
-0.343 | 1.0 | N | 0.723 | 0.426 | 0.43912465853 | gnomAD-4.0.0 | 6.4092E-06 | None | None | None | None | N | None | 8.45909E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1827 | likely_benign | 0.2737 | benign | -0.187 | Destabilizing | 1.0 | D | 0.754 | deleterious | N | 0.502866067 | None | None | N |
| D/C | 0.7939 | likely_pathogenic | 0.8933 | pathogenic | -0.142 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | N |
| D/E | 0.2039 | likely_benign | 0.2867 | benign | -0.256 | Destabilizing | 1.0 | D | 0.525 | neutral | N | 0.507655115 | None | None | N |
| D/F | 0.6941 | likely_pathogenic | 0.7999 | pathogenic | 0.044 | Stabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| D/G | 0.2139 | likely_benign | 0.3081 | benign | -0.402 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | N | 0.507447294 | None | None | N |
| D/H | 0.4321 | ambiguous | 0.6198 | pathogenic | 0.312 | Stabilizing | 1.0 | D | 0.698 | prob.neutral | D | 0.614979719 | None | None | N |
| D/I | 0.4535 | ambiguous | 0.5867 | pathogenic | 0.337 | Stabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| D/K | 0.4652 | ambiguous | 0.6722 | pathogenic | 0.283 | Stabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| D/L | 0.4505 | ambiguous | 0.6082 | pathogenic | 0.337 | Stabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| D/M | 0.6844 | likely_pathogenic | 0.809 | pathogenic | 0.292 | Stabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| D/N | 0.1206 | likely_benign | 0.1419 | benign | -0.147 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | N | 0.504853214 | None | None | N |
| D/P | 0.5223 | ambiguous | 0.7042 | pathogenic | 0.185 | Stabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | N |
| D/Q | 0.4688 | ambiguous | 0.6667 | pathogenic | -0.078 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| D/R | 0.5391 | ambiguous | 0.7479 | pathogenic | 0.546 | Stabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| D/S | 0.1851 | likely_benign | 0.2465 | benign | -0.245 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| D/T | 0.3045 | likely_benign | 0.4227 | ambiguous | -0.069 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| D/V | 0.2541 | likely_benign | 0.3584 | ambiguous | 0.185 | Stabilizing | 1.0 | D | 0.751 | deleterious | D | 0.596752704 | None | None | N |
| D/W | 0.9232 | likely_pathogenic | 0.9672 | pathogenic | 0.199 | Stabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| D/Y | 0.2652 | likely_benign | 0.3883 | ambiguous | 0.287 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | D | 0.693507859 | 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.