Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23853 | 71782;71783;71784 | chr2:178574575;178574574;178574573 | chr2:179439302;179439301;179439300 |
| N2AB | 22212 | 66859;66860;66861 | chr2:178574575;178574574;178574573 | chr2:179439302;179439301;179439300 |
| N2A | 21285 | 64078;64079;64080 | chr2:178574575;178574574;178574573 | chr2:179439302;179439301;179439300 |
| N2B | 14788 | 44587;44588;44589 | chr2:178574575;178574574;178574573 | chr2:179439302;179439301;179439300 |
| Novex-1 | 14913 | 44962;44963;44964 | chr2:178574575;178574574;178574573 | chr2:179439302;179439301;179439300 |
| Novex-2 | 14980 | 45163;45164;45165 | chr2:178574575;178574574;178574573 | chr2:179439302;179439301;179439300 |
| 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 | None | None | 1.0 | N | 0.643 | 0.523 | 0.520373764981 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| D/N | rs1387991752  |
None | 1.0 | N | 0.688 | 0.357 | 0.406531046227 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs1387991752 |
None | 1.0 | N | 0.688 | 0.357 | 0.406531046227 | gnomAD-4.0.0 | 2.03E-06 | None | None | None | None | I | None | 3.49418E-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 | 0.6413 | likely_pathogenic | 0.6932 | pathogenic | -0.411 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | N | 0.497172495 | None | None | I |
| D/C | 0.9157 | likely_pathogenic | 0.9338 | pathogenic | 0.175 | Stabilizing | 1.0 | D | 0.652 | neutral | None | None | None | None | I |
| D/E | 0.7473 | likely_pathogenic | 0.7567 | pathogenic | -0.361 | Destabilizing | 1.0 | D | 0.449 | neutral | N | 0.500931477 | None | None | I |
| D/F | 0.9514 | likely_pathogenic | 0.9587 | pathogenic | -0.499 | Destabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | I |
| D/G | 0.593 | likely_pathogenic | 0.6311 | pathogenic | -0.622 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | N | 0.508733065 | None | None | I |
| D/H | 0.7577 | likely_pathogenic | 0.7797 | pathogenic | -0.659 | Destabilizing | 1.0 | D | 0.643 | neutral | N | 0.505668418 | None | None | I |
| D/I | 0.9069 | likely_pathogenic | 0.9149 | pathogenic | 0.103 | Stabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | I |
| D/K | 0.8809 | likely_pathogenic | 0.9062 | pathogenic | 0.33 | Stabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| D/L | 0.8861 | likely_pathogenic | 0.9054 | pathogenic | 0.103 | Stabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | I |
| D/M | 0.9427 | likely_pathogenic | 0.9495 | pathogenic | 0.48 | Stabilizing | 1.0 | D | 0.64 | neutral | None | None | None | None | I |
| D/N | 0.1221 | likely_benign | 0.1361 | benign | 0.038 | Stabilizing | 1.0 | D | 0.688 | prob.neutral | N | 0.511459616 | None | None | I |
| D/P | 0.9371 | likely_pathogenic | 0.9478 | pathogenic | -0.046 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | I |
| D/Q | 0.8679 | likely_pathogenic | 0.8892 | pathogenic | 0.072 | Stabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | I |
| D/R | 0.8898 | likely_pathogenic | 0.9075 | pathogenic | 0.284 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | I |
| D/S | 0.2695 | likely_benign | 0.2993 | benign | -0.072 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| D/T | 0.4578 | ambiguous | 0.4809 | ambiguous | 0.101 | Stabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | I |
| D/V | 0.7784 | likely_pathogenic | 0.7922 | pathogenic | -0.046 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | D | 0.526886545 | None | None | I |
| D/W | 0.9922 | likely_pathogenic | 0.9928 | pathogenic | -0.392 | Destabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | I |
| D/Y | 0.7309 | likely_pathogenic | 0.7627 | pathogenic | -0.265 | Destabilizing | 1.0 | D | 0.628 | neutral | D | 0.539510298 | None | None | I |
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.