Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27180 | 81763;81764;81765 | chr2:178564594;178564593;178564592 | chr2:179429321;179429320;179429319 |
| N2AB | 25539 | 76840;76841;76842 | chr2:178564594;178564593;178564592 | chr2:179429321;179429320;179429319 |
| N2A | 24612 | 74059;74060;74061 | chr2:178564594;178564593;178564592 | chr2:179429321;179429320;179429319 |
| N2B | 18115 | 54568;54569;54570 | chr2:178564594;178564593;178564592 | chr2:179429321;179429320;179429319 |
| Novex-1 | 18240 | 54943;54944;54945 | chr2:178564594;178564593;178564592 | chr2:179429321;179429320;179429319 |
| Novex-2 | 18307 | 55144;55145;55146 | chr2:178564594;178564593;178564592 | chr2:179429321;179429320;179429319 |
| 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 | rs182126530  |
-0.931 | 0.025 | N | 0.278 | 0.321 | None | gnomAD-2.1.1 | 7.43883E-04 | None | None | None | None | N | None | 5.3341E-03 | 4.24953E-04 | None | 0 | 0 | None | 1.76517E-03 | None | 0 | 5.48E-05 | 4.22535E-04 |
| I/T | rs182126530 |
-0.931 | 0.025 | N | 0.278 | 0.321 | None | gnomAD-3.1.2 | 1.72906E-03 | None | None | None | None | N | None | 5.64835E-03 | 1.11402E-03 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 1.03648E-03 | 1.43403E-03 |
| I/T | rs182126530 |
-0.931 | 0.025 | N | 0.278 | 0.321 | None | 1000 genomes | 9.98403E-04 | None | None | None | None | N | None | 3.8E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/T | rs182126530 |
-0.931 | 0.025 | N | 0.278 | 0.321 | None | gnomAD-4.0.0 | 4.67309E-04 | None | None | None | None | N | None | 6.34582E-03 | 5.83606E-04 | None | 0 | 0 | None | 0 | 6.59848E-04 | 3.56025E-05 | 1.68003E-03 | 7.04496E-04 |
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 | 0.1981 | likely_benign | 0.1941 | benign | -1.023 | Destabilizing | 0.845 | D | 0.529 | neutral | None | None | None | None | N |
| I/C | 0.7077 | likely_pathogenic | 0.7213 | pathogenic | -0.706 | Destabilizing | 0.999 | D | 0.636 | neutral | None | None | None | None | N |
| I/D | 0.7457 | likely_pathogenic | 0.7101 | pathogenic | -0.477 | Destabilizing | 0.975 | D | 0.704 | prob.neutral | None | None | None | None | N |
| I/E | 0.5844 | likely_pathogenic | 0.5381 | ambiguous | -0.536 | Destabilizing | 0.975 | D | 0.7 | prob.neutral | None | None | None | None | N |
| I/F | 0.1958 | likely_benign | 0.1829 | benign | -0.781 | Destabilizing | 0.983 | D | 0.565 | neutral | D | 0.524234125 | None | None | N |
| I/G | 0.6231 | likely_pathogenic | 0.6174 | pathogenic | -1.25 | Destabilizing | 0.975 | D | 0.661 | neutral | None | None | None | None | N |
| I/H | 0.6155 | likely_pathogenic | 0.5911 | pathogenic | -0.387 | Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | N |
| I/K | 0.4938 | ambiguous | 0.4425 | ambiguous | -0.673 | Destabilizing | 0.975 | D | 0.703 | prob.neutral | None | None | None | None | N |
| I/L | 0.1212 | likely_benign | 0.1135 | benign | -0.523 | Destabilizing | 0.63 | D | 0.331 | neutral | N | 0.408004387 | None | None | N |
| I/M | 0.1006 | likely_benign | 0.099 | benign | -0.482 | Destabilizing | 0.994 | D | 0.541 | neutral | N | 0.512843696 | None | None | N |
| I/N | 0.3923 | ambiguous | 0.363 | ambiguous | -0.48 | Destabilizing | 0.967 | D | 0.719 | prob.delet. | N | 0.469722943 | None | None | N |
| I/P | 0.8858 | likely_pathogenic | 0.8819 | pathogenic | -0.656 | Destabilizing | 0.987 | D | 0.723 | prob.delet. | None | None | None | None | N |
| I/Q | 0.5385 | ambiguous | 0.5072 | ambiguous | -0.703 | Destabilizing | 0.987 | D | 0.727 | prob.delet. | None | None | None | None | N |
| I/R | 0.4016 | ambiguous | 0.3499 | ambiguous | -0.038 | Destabilizing | 0.975 | D | 0.721 | prob.delet. | None | None | None | None | N |
| I/S | 0.2771 | likely_benign | 0.2594 | benign | -0.989 | Destabilizing | 0.805 | D | 0.563 | neutral | N | 0.454176607 | None | None | N |
| I/T | 0.0997 | likely_benign | 0.0938 | benign | -0.94 | Destabilizing | 0.025 | N | 0.278 | neutral | N | 0.408713676 | None | None | N |
| I/V | 0.059 | likely_benign | 0.0628 | benign | -0.656 | Destabilizing | 0.426 | N | 0.321 | neutral | N | 0.410793976 | None | None | N |
| I/W | 0.8194 | likely_pathogenic | 0.8005 | pathogenic | -0.794 | Destabilizing | 0.999 | D | 0.73 | prob.delet. | None | None | None | None | N |
| I/Y | 0.6251 | likely_pathogenic | 0.6093 | pathogenic | -0.574 | Destabilizing | 0.996 | D | 0.644 | 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.