Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24465 | 73618;73619;73620 | chr2:178572739;178572738;178572737 | chr2:179437466;179437465;179437464 |
| N2AB | 22824 | 68695;68696;68697 | chr2:178572739;178572738;178572737 | chr2:179437466;179437465;179437464 |
| N2A | 21897 | 65914;65915;65916 | chr2:178572739;178572738;178572737 | chr2:179437466;179437465;179437464 |
| N2B | 15400 | 46423;46424;46425 | chr2:178572739;178572738;178572737 | chr2:179437466;179437465;179437464 |
| Novex-1 | 15525 | 46798;46799;46800 | chr2:178572739;178572738;178572737 | chr2:179437466;179437465;179437464 |
| Novex-2 | 15592 | 46999;47000;47001 | chr2:178572739;178572738;178572737 | chr2:179437466;179437465;179437464 |
| 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 | rs764857452  |
-0.567 | 0.001 | N | 0.347 | 0.162 | 0.162503812791 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.78E-05 | 0 |
| D/N | rs764857452 |
-0.567 | 0.001 | N | 0.347 | 0.162 | 0.162503812791 | gnomAD-4.0.0 | 1.1143E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.42976E-05 | 2.8659E-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 | 0.1191 | likely_benign | 0.1309 | benign | -0.381 | Destabilizing | None | N | 0.296 | neutral | N | 0.415540861 | None | None | N |
| D/C | 0.5208 | ambiguous | 0.5894 | pathogenic | -0.157 | Destabilizing | 0.316 | N | 0.563 | neutral | None | None | None | None | N |
| D/E | 0.0559 | likely_benign | 0.0621 | benign | -0.424 | Destabilizing | None | N | 0.14 | neutral | N | 0.402744922 | None | None | N |
| D/F | 0.4817 | ambiguous | 0.5352 | ambiguous | -0.194 | Destabilizing | 0.116 | N | 0.582 | neutral | None | None | None | None | N |
| D/G | 0.1172 | likely_benign | 0.1348 | benign | -0.622 | Destabilizing | 0.001 | N | 0.387 | neutral | N | 0.453074955 | None | None | N |
| D/H | 0.2913 | likely_benign | 0.3241 | benign | -0.147 | Destabilizing | 0.032 | N | 0.525 | neutral | N | 0.473563468 | None | None | N |
| D/I | 0.1985 | likely_benign | 0.2219 | benign | 0.221 | Stabilizing | 0.018 | N | 0.521 | neutral | None | None | None | None | N |
| D/K | 0.2394 | likely_benign | 0.2852 | benign | -0.083 | Destabilizing | None | N | 0.233 | neutral | None | None | None | None | N |
| D/L | 0.2035 | likely_benign | 0.2276 | benign | 0.221 | Stabilizing | 0.004 | N | 0.444 | neutral | None | None | None | None | N |
| D/M | 0.3393 | likely_benign | 0.3925 | ambiguous | 0.367 | Stabilizing | 0.316 | N | 0.605 | neutral | None | None | None | None | N |
| D/N | 0.1169 | likely_benign | 0.1233 | benign | -0.336 | Destabilizing | 0.001 | N | 0.347 | neutral | N | 0.435217126 | None | None | N |
| D/P | 0.4101 | ambiguous | 0.454 | ambiguous | 0.043 | Stabilizing | 0.008 | N | 0.362 | neutral | None | None | None | None | N |
| D/Q | 0.1644 | likely_benign | 0.1932 | benign | -0.281 | Destabilizing | 0.001 | N | 0.208 | neutral | None | None | None | None | N |
| D/R | 0.3232 | likely_benign | 0.3739 | ambiguous | 0.172 | Stabilizing | 0.001 | N | 0.433 | neutral | None | None | None | None | N |
| D/S | 0.1117 | likely_benign | 0.1203 | benign | -0.499 | Destabilizing | 0.001 | N | 0.199 | neutral | None | None | None | None | N |
| D/T | 0.1731 | likely_benign | 0.1906 | benign | -0.316 | Destabilizing | 0.002 | N | 0.383 | neutral | None | None | None | None | N |
| D/V | 0.1239 | likely_benign | 0.1336 | benign | 0.043 | Stabilizing | 0.003 | N | 0.455 | neutral | N | 0.467239118 | None | None | N |
| D/W | 0.8028 | likely_pathogenic | 0.8459 | pathogenic | -0.045 | Destabilizing | 0.316 | N | 0.563 | neutral | None | None | None | None | N |
| D/Y | 0.2414 | likely_benign | 0.2718 | benign | 0.031 | Stabilizing | 0.039 | N | 0.556 | neutral | N | 0.473816958 | 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.