Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20956 | 63091;63092;63093 | chr2:178588859;178588858;178588857 | chr2:179453586;179453585;179453584 |
| N2AB | 19315 | 58168;58169;58170 | chr2:178588859;178588858;178588857 | chr2:179453586;179453585;179453584 |
| N2A | 18388 | 55387;55388;55389 | chr2:178588859;178588858;178588857 | chr2:179453586;179453585;179453584 |
| N2B | 11891 | 35896;35897;35898 | chr2:178588859;178588858;178588857 | chr2:179453586;179453585;179453584 |
| Novex-1 | 12016 | 36271;36272;36273 | chr2:178588859;178588858;178588857 | chr2:179453586;179453585;179453584 |
| Novex-2 | 12083 | 36472;36473;36474 | chr2:178588859;178588858;178588857 | chr2:179453586;179453585;179453584 |
| 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/T | rs758926314  |
-2.591 | 0.003 | N | 0.341 | 0.219 | 0.497613835824 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| I/T | rs758926314 |
-2.591 | 0.003 | N | 0.341 | 0.219 | 0.497613835824 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs758926314 |
-2.591 | 0.003 | N | 0.341 | 0.219 | 0.497613835824 | gnomAD-4.0.0 | 2.54147E-05 | None | None | None | None | N | None | 2.67051E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.22135E-05 | 0 | 1.60159E-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 | 0.1775 | likely_benign | 0.1716 | benign | -1.081 | Destabilizing | 0.134 | N | 0.629 | neutral | None | None | None | None | N |
| I/C | 0.5751 | likely_pathogenic | 0.5391 | ambiguous | -0.759 | Destabilizing | 0.953 | D | 0.673 | prob.neutral | None | None | None | None | N |
| I/D | 0.7402 | likely_pathogenic | 0.6858 | pathogenic | -0.427 | Destabilizing | 0.842 | D | 0.818 | deleterious | None | None | None | None | N |
| I/E | 0.5032 | ambiguous | 0.4411 | ambiguous | -0.468 | Destabilizing | 0.842 | D | 0.787 | deleterious | None | None | None | None | N |
| I/F | 0.156 | likely_benign | 0.1381 | benign | -0.755 | Destabilizing | 0.724 | D | 0.771 | deleterious | None | None | None | None | N |
| I/G | 0.6066 | likely_pathogenic | 0.5881 | pathogenic | -1.335 | Destabilizing | 0.603 | D | 0.762 | deleterious | None | None | None | None | N |
| I/H | 0.4559 | ambiguous | 0.4118 | ambiguous | -0.482 | Destabilizing | 0.984 | D | 0.785 | deleterious | None | None | None | None | N |
| I/K | 0.2931 | likely_benign | 0.2705 | benign | -0.7 | Destabilizing | 0.8 | D | 0.803 | deleterious | N | 0.508760453 | None | None | N |
| I/L | 0.0974 | likely_benign | 0.0956 | benign | -0.498 | Destabilizing | 0.048 | N | 0.503 | neutral | N | 0.481400494 | None | None | N |
| I/M | 0.0869 | likely_benign | 0.0863 | benign | -0.477 | Destabilizing | 0.664 | D | 0.677 | prob.neutral | N | 0.520228241 | None | None | N |
| I/N | 0.3273 | likely_benign | 0.3001 | benign | -0.517 | Destabilizing | 0.842 | D | 0.83 | deleterious | None | None | None | None | N |
| I/P | 0.5134 | ambiguous | 0.5078 | ambiguous | -0.659 | Destabilizing | 0.942 | D | 0.834 | deleterious | None | None | None | None | N |
| I/Q | 0.3338 | likely_benign | 0.3106 | benign | -0.709 | Destabilizing | 0.942 | D | 0.857 | deleterious | None | None | None | None | N |
| I/R | 0.2317 | likely_benign | 0.206 | benign | -0.103 | Destabilizing | 0.8 | D | 0.851 | deleterious | N | 0.47090735 | None | None | N |
| I/S | 0.2495 | likely_benign | 0.2341 | benign | -1.072 | Destabilizing | 0.272 | N | 0.675 | prob.neutral | None | None | None | None | N |
| I/T | 0.0854 | likely_benign | 0.0851 | benign | -0.997 | Destabilizing | 0.003 | N | 0.341 | neutral | N | 0.468372455 | None | None | N |
| I/V | 0.0623 | likely_benign | 0.0622 | benign | -0.659 | Destabilizing | 0.001 | N | 0.125 | neutral | N | 0.417927805 | None | None | N |
| I/W | 0.7314 | likely_pathogenic | 0.6909 | pathogenic | -0.779 | Destabilizing | 0.984 | D | 0.805 | deleterious | None | None | None | None | N |
| I/Y | 0.4935 | ambiguous | 0.4306 | ambiguous | -0.557 | Destabilizing | 0.842 | D | 0.782 | 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.