Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22654 | 68185;68186;68187 | chr2:178579070;178579069;178579068 | chr2:179443797;179443796;179443795 |
| N2AB | 21013 | 63262;63263;63264 | chr2:178579070;178579069;178579068 | chr2:179443797;179443796;179443795 |
| N2A | 20086 | 60481;60482;60483 | chr2:178579070;178579069;178579068 | chr2:179443797;179443796;179443795 |
| N2B | 13589 | 40990;40991;40992 | chr2:178579070;178579069;178579068 | chr2:179443797;179443796;179443795 |
| Novex-1 | 13714 | 41365;41366;41367 | chr2:178579070;178579069;178579068 | chr2:179443797;179443796;179443795 |
| Novex-2 | 13781 | 41566;41567;41568 | chr2:178579070;178579069;178579068 | chr2:179443797;179443796;179443795 |
| 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/H | rs144295295  |
-0.515 | 0.931 | N | 0.694 | 0.267 | None | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 3.367E-04 | None | 0 | None | 0 | 0 | 0 |
| D/H | rs144295295 |
-0.515 | 0.931 | N | 0.694 | 0.267 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 9.7012E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/H | rs144295295 |
-0.515 | 0.931 | N | 0.694 | 0.267 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 2E-03 | 0 | None | None | None | 0 | None |
| D/H | rs144295295 |
-0.515 | 0.931 | N | 0.694 | 0.267 | None | gnomAD-4.0.0 | 1.2689E-04 | None | None | None | None | N | None | 0 | 1.69492E-05 | None | 0 | 2.36113E-03 | None | 0 | 0 | 0 | 0 | 2.84414E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1238 | likely_benign | 0.1184 | benign | -0.368 | Destabilizing | 0.201 | N | 0.555 | neutral | N | 0.486387813 | None | None | N |
| D/C | 0.4659 | ambiguous | 0.4216 | ambiguous | -0.133 | Destabilizing | 0.982 | D | 0.747 | deleterious | None | None | None | None | N |
| D/E | 0.08 | likely_benign | 0.0844 | benign | -0.464 | Destabilizing | 0.002 | N | 0.175 | neutral | N | 0.456256907 | None | None | N |
| D/F | 0.512 | ambiguous | 0.4743 | ambiguous | -0.134 | Destabilizing | 0.935 | D | 0.761 | deleterious | None | None | None | None | N |
| D/G | 0.1652 | likely_benign | 0.1524 | benign | -0.635 | Destabilizing | 0.334 | N | 0.572 | neutral | N | 0.497316883 | None | None | N |
| D/H | 0.216 | likely_benign | 0.1919 | benign | -0.216 | Destabilizing | 0.931 | D | 0.694 | prob.neutral | N | 0.513478414 | None | None | N |
| D/I | 0.2204 | likely_benign | 0.2102 | benign | 0.305 | Stabilizing | 0.826 | D | 0.779 | deleterious | None | None | None | None | N |
| D/K | 0.2659 | likely_benign | 0.2457 | benign | -0.063 | Destabilizing | 0.25 | N | 0.619 | neutral | None | None | None | None | N |
| D/L | 0.2466 | likely_benign | 0.2428 | benign | 0.305 | Stabilizing | 0.7 | D | 0.755 | deleterious | None | None | None | None | N |
| D/M | 0.3932 | ambiguous | 0.3713 | ambiguous | 0.509 | Stabilizing | 0.982 | D | 0.735 | prob.delet. | None | None | None | None | N |
| D/N | 0.1009 | likely_benign | 0.0893 | benign | -0.411 | Destabilizing | 0.334 | N | 0.549 | neutral | N | 0.502357343 | None | None | N |
| D/P | 0.8056 | likely_pathogenic | 0.8031 | pathogenic | 0.105 | Stabilizing | 0.826 | D | 0.729 | prob.delet. | None | None | None | None | N |
| D/Q | 0.2066 | likely_benign | 0.1943 | benign | -0.33 | Destabilizing | 0.539 | D | 0.598 | neutral | None | None | None | None | N |
| D/R | 0.3262 | likely_benign | 0.2918 | benign | 0.136 | Stabilizing | 0.539 | D | 0.757 | deleterious | None | None | None | None | N |
| D/S | 0.0874 | likely_benign | 0.0815 | benign | -0.561 | Destabilizing | 0.057 | N | 0.233 | neutral | None | None | None | None | N |
| D/T | 0.1399 | likely_benign | 0.1328 | benign | -0.353 | Destabilizing | 0.25 | N | 0.637 | neutral | None | None | None | None | N |
| D/V | 0.1354 | likely_benign | 0.134 | benign | 0.105 | Stabilizing | 0.638 | D | 0.756 | deleterious | N | 0.459009211 | None | None | N |
| D/W | 0.7921 | likely_pathogenic | 0.7698 | pathogenic | 0.021 | Stabilizing | 0.982 | D | 0.706 | prob.neutral | None | None | None | None | N |
| D/Y | 0.2223 | likely_benign | 0.2006 | benign | 0.093 | Stabilizing | 0.976 | D | 0.757 | deleterious | N | 0.497490241 | 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.