Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15574 | 46945;46946;46947 | chr2:178618830;178618829;178618828 | chr2:179483557;179483556;179483555 |
| N2AB | 13933 | 42022;42023;42024 | chr2:178618830;178618829;178618828 | chr2:179483557;179483556;179483555 |
| N2A | 13006 | 39241;39242;39243 | chr2:178618830;178618829;178618828 | chr2:179483557;179483556;179483555 |
| N2B | 6509 | 19750;19751;19752 | chr2:178618830;178618829;178618828 | chr2:179483557;179483556;179483555 |
| Novex-1 | 6634 | 20125;20126;20127 | chr2:178618830;178618829;178618828 | chr2:179483557;179483556;179483555 |
| Novex-2 | 6701 | 20326;20327;20328 | chr2:178618830;178618829;178618828 | chr2:179483557;179483556;179483555 |
| 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 | rs1328343991  |
None | 1.0 | N | 0.594 | 0.398 | 0.314417295294 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs1328343991 |
None | 1.0 | N | 0.594 | 0.398 | 0.314417295294 | gnomAD-4.0.0 | 6.58163E-06 | None | None | None | None | N | None | 2.41371E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | None | None | 1.0 | N | 0.737 | 0.515 | 0.323615622048 | gnomAD-4.0.0 | 1.60031E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43964E-05 | 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 | 0.3141 | likely_benign | 0.3607 | ambiguous | -0.653 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | N | 0.435846571 | None | None | N |
| D/C | 0.7688 | likely_pathogenic | 0.8198 | pathogenic | -0.203 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| D/E | 0.2553 | likely_benign | 0.2907 | benign | -0.539 | Destabilizing | 1.0 | D | 0.398 | neutral | N | 0.437842848 | None | None | N |
| D/F | 0.7175 | likely_pathogenic | 0.7553 | pathogenic | -0.422 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| D/G | 0.2732 | likely_benign | 0.3124 | benign | -0.914 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | N | 0.438101989 | None | None | N |
| D/H | 0.4528 | ambiguous | 0.5338 | ambiguous | -0.535 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | N | 0.439028274 | None | None | N |
| D/I | 0.569 | likely_pathogenic | 0.6213 | pathogenic | 0.013 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| D/K | 0.5445 | ambiguous | 0.5968 | pathogenic | -0.143 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | N |
| D/L | 0.5422 | ambiguous | 0.5833 | pathogenic | 0.013 | Stabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | N |
| D/M | 0.7615 | likely_pathogenic | 0.8036 | pathogenic | 0.326 | Stabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| D/N | 0.1221 | likely_benign | 0.1512 | benign | -0.483 | Destabilizing | 1.0 | D | 0.594 | neutral | N | 0.438101989 | None | None | N |
| D/P | 0.6756 | likely_pathogenic | 0.6741 | pathogenic | -0.186 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | N |
| D/Q | 0.5 | ambiguous | 0.5405 | ambiguous | -0.427 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| D/R | 0.596 | likely_pathogenic | 0.6512 | pathogenic | 0.035 | Stabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | N |
| D/S | 0.1853 | likely_benign | 0.2228 | benign | -0.643 | Destabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | N |
| D/T | 0.386 | ambiguous | 0.4401 | ambiguous | -0.438 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| D/V | 0.403 | ambiguous | 0.444 | ambiguous | -0.186 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | N | 0.435005454 | None | None | N |
| D/W | 0.9284 | likely_pathogenic | 0.9372 | pathogenic | -0.21 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | N |
| D/Y | 0.3974 | ambiguous | 0.4289 | ambiguous | -0.18 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.438101989 | 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.