Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6335 | 19228;19229;19230 | chr2:178729035;178729034;178729033 | chr2:179593762;179593761;179593760 |
| N2AB | 6018 | 18277;18278;18279 | chr2:178729035;178729034;178729033 | chr2:179593762;179593761;179593760 |
| N2A | 5091 | 15496;15497;15498 | chr2:178729035;178729034;178729033 | chr2:179593762;179593761;179593760 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/G | rs72648951  |
0.386 | 0.001 | N | 0.301 | 0.104 | None | gnomAD-2.1.1 | 3.03735E-03 | None | None | None | None | I | None | 3.22379E-02 | 1.33819E-03 | None | 0 | 0 | None | 6.57E-05 | None | 0 | 7.11E-05 | 1.56383E-03 |
| D/G | rs72648951 |
0.386 | 0.001 | N | 0.301 | 0.104 | None | gnomAD-3.1.2 | 9.37455E-03 | None | None | None | None | I | None | 3.2413E-02 | 3.53774E-03 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 5.88E-05 | 2.06782E-04 | 1.09838E-02 |
| D/G | rs72648951 |
0.386 | 0.001 | N | 0.301 | 0.104 | None | 1000 genomes | 9.1853E-03 | None | None | None | None | I | None | 3.25E-02 | 4.3E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| D/G | rs72648951 |
0.386 | 0.001 | N | 0.301 | 0.104 | None | gnomAD-4.0.0 | 1.66469E-03 | None | None | None | None | I | None | 3.14917E-02 | 2.15481E-03 | None | 0 | 0 | None | 0 | 4.95704E-04 | 2.79797E-05 | 6.59413E-05 | 2.4348E-03 |
| D/N | rs1346291126 |
0.708 | 0.002 | N | 0.217 | 0.072 | 0.126345400529 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.99E-06 | 0 |
| D/N | rs1346291126 |
0.708 | 0.002 | N | 0.217 | 0.072 | 0.126345400529 | gnomAD-4.0.0 | 1.36926E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79948E-06 | 0 | 0 |
| D/V | None | None | 0.497 | N | 0.517 | 0.214 | 0.471292358255 | gnomAD-4.0.0 | 1.36923E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79947E-06 | 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 | 0.145 | likely_benign | 0.1317 | benign | -0.073 | Destabilizing | 0.124 | N | 0.454 | neutral | N | 0.510024316 | None | None | I |
| D/C | 0.4971 | ambiguous | 0.4615 | ambiguous | 0.292 | Stabilizing | 0.968 | D | 0.617 | neutral | None | None | None | None | I |
| D/E | 0.1989 | likely_benign | 0.1814 | benign | -0.248 | Destabilizing | 0.124 | N | 0.417 | neutral | N | 0.503039629 | None | None | I |
| D/F | 0.4948 | ambiguous | 0.4616 | ambiguous | -0.288 | Destabilizing | 0.89 | D | 0.561 | neutral | None | None | None | None | I |
| D/G | 0.0907 | likely_benign | 0.0996 | benign | -0.232 | Destabilizing | 0.001 | N | 0.301 | neutral | N | 0.456707119 | None | None | I |
| D/H | 0.2414 | likely_benign | 0.2198 | benign | -0.172 | Destabilizing | 0.788 | D | 0.445 | neutral | N | 0.467190231 | None | None | I |
| D/I | 0.3476 | ambiguous | 0.3183 | benign | 0.282 | Stabilizing | 0.567 | D | 0.549 | neutral | None | None | None | None | I |
| D/K | 0.2714 | likely_benign | 0.2377 | benign | 0.467 | Stabilizing | 0.396 | N | 0.4 | neutral | None | None | None | None | I |
| D/L | 0.3305 | likely_benign | 0.3052 | benign | 0.282 | Stabilizing | 0.567 | D | 0.524 | neutral | None | None | None | None | I |
| D/M | 0.4925 | ambiguous | 0.4644 | ambiguous | 0.445 | Stabilizing | 0.968 | D | 0.587 | neutral | None | None | None | None | I |
| D/N | 0.0767 | likely_benign | 0.0756 | benign | 0.371 | Stabilizing | 0.002 | N | 0.217 | neutral | N | 0.492014558 | None | None | I |
| D/P | 0.7306 | likely_pathogenic | 0.6787 | pathogenic | 0.186 | Stabilizing | 0.726 | D | 0.427 | neutral | None | None | None | None | I |
| D/Q | 0.3116 | likely_benign | 0.2744 | benign | 0.36 | Stabilizing | 0.567 | D | 0.396 | neutral | None | None | None | None | I |
| D/R | 0.3179 | likely_benign | 0.2748 | benign | 0.513 | Stabilizing | 0.567 | D | 0.509 | neutral | None | None | None | None | I |
| D/S | 0.0992 | likely_benign | 0.0947 | benign | 0.249 | Stabilizing | 0.157 | N | 0.405 | neutral | None | None | None | None | I |
| D/T | 0.1626 | likely_benign | 0.1516 | benign | 0.362 | Stabilizing | 0.011 | N | 0.293 | neutral | None | None | None | None | I |
| D/V | 0.2098 | likely_benign | 0.1914 | benign | 0.186 | Stabilizing | 0.497 | N | 0.517 | neutral | N | 0.479053516 | None | None | I |
| D/W | 0.8058 | likely_pathogenic | 0.7627 | pathogenic | -0.267 | Destabilizing | 0.968 | D | 0.676 | prob.neutral | None | None | None | None | I |
| D/Y | 0.2158 | likely_benign | 0.1925 | benign | -0.07 | Destabilizing | 0.859 | D | 0.56 | neutral | N | 0.505551562 | 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.