Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7815 | 23668;23669;23670 | chr2:178720199;178720198;178720197 | chr2:179584926;179584925;179584924 |
| N2AB | 7498 | 22717;22718;22719 | chr2:178720199;178720198;178720197 | chr2:179584926;179584925;179584924 |
| N2A | 6571 | 19936;19937;19938 | chr2:178720199;178720198;178720197 | chr2:179584926;179584925;179584924 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | None | None | 0.058 | N | 0.424 | 0.273 | 0.591730238936 | gnomAD-4.0.0 | 6.84262E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99523E-07 | 0 | 0 |
| R/P | None | None | 0.232 | N | 0.527 | 0.284 | 0.183819452728 | gnomAD-4.0.0 | 6.8426E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99518E-07 | 0 | 0 |
| R/Q | rs372804810  |
0.155 | None | N | 0.213 | 0.137 | None | gnomAD-2.1.1 | 4.03E-05 | None | None | None | None | I | None | 0 | 8.7E-05 | None | 0 | 5.57E-05 | None | 3.27E-05 | None | 0 | 4.46E-05 | 0 |
| R/Q | rs372804810 |
0.155 | None | N | 0.213 | 0.137 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | I | None | 0 | 2.61814E-04 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/Q | rs372804810 |
0.155 | None | N | 0.213 | 0.137 | None | gnomAD-4.0.0 | 3.40853E-05 | None | None | None | None | I | None | 0 | 1.667E-04 | None | 0 | 8.91544E-05 | None | 1.56279E-05 | 1.64474E-04 | 2.79726E-05 | 3.29381E-05 | 4.80384E-05 |
| R/W | rs528264100 |
-0.106 | 0.964 | N | 0.471 | 0.336 | 0.55355060856 | gnomAD-2.1.1 | 4.03E-05 | None | None | None | None | I | None | 6.47E-05 | 8.7E-05 | None | 9.97E-05 | 0 | None | 6.54E-05 | None | 0 | 2.68E-05 | 0 |
| R/W | rs528264100 |
-0.106 | 0.964 | N | 0.471 | 0.336 | 0.55355060856 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.92901E-04 | None | 0 | 0 | 1.47E-05 | 2.06782E-04 | 4.78927E-04 |
| R/W | rs528264100 |
-0.106 | 0.964 | N | 0.471 | 0.336 | 0.55355060856 | gnomAD-4.0.0 | 2.29286E-05 | None | None | None | None | I | None | 1.33294E-05 | 1.16674E-04 | None | 3.37838E-05 | 4.45871E-05 | None | 0 | 3.30142E-04 | 1.35626E-05 | 6.5879E-05 | 3.20133E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.1826 | likely_benign | 0.1705 | benign | -0.576 | Destabilizing | 0.007 | N | 0.325 | neutral | None | None | None | None | I |
| R/C | 0.1594 | likely_benign | 0.1432 | benign | -0.559 | Destabilizing | 0.864 | D | 0.473 | neutral | None | None | None | None | I |
| R/D | 0.3704 | ambiguous | 0.3365 | benign | -0.034 | Destabilizing | 0.072 | N | 0.497 | neutral | None | None | None | None | I |
| R/E | 0.1281 | likely_benign | 0.1208 | benign | 0.113 | Stabilizing | 0.007 | N | 0.279 | neutral | None | None | None | None | I |
| R/F | 0.397 | ambiguous | 0.3461 | ambiguous | -0.276 | Destabilizing | 0.038 | N | 0.525 | neutral | None | None | None | None | I |
| R/G | 0.1326 | likely_benign | 0.1272 | benign | -0.907 | Destabilizing | 0.058 | N | 0.424 | neutral | N | 0.493674437 | None | None | I |
| R/H | 0.0776 | likely_benign | 0.0741 | benign | -1.3 | Destabilizing | 0.214 | N | 0.409 | neutral | None | None | None | None | I |
| R/I | 0.175 | likely_benign | 0.1658 | benign | 0.315 | Stabilizing | 0.038 | N | 0.525 | neutral | None | None | None | None | I |
| R/K | 0.0737 | likely_benign | 0.072 | benign | -0.58 | Destabilizing | None | N | 0.197 | neutral | None | None | None | None | I |
| R/L | 0.1399 | likely_benign | 0.1259 | benign | 0.315 | Stabilizing | None | N | 0.309 | neutral | N | 0.435954285 | None | None | I |
| R/M | 0.1753 | likely_benign | 0.1629 | benign | -0.2 | Destabilizing | 0.214 | N | 0.467 | neutral | None | None | None | None | I |
| R/N | 0.2858 | likely_benign | 0.2404 | benign | -0.232 | Destabilizing | 0.072 | N | 0.366 | neutral | None | None | None | None | I |
| R/P | 0.6421 | likely_pathogenic | 0.6009 | pathogenic | 0.04 | Stabilizing | 0.232 | N | 0.527 | neutral | N | 0.480841212 | None | None | I |
| R/Q | 0.0594 | likely_benign | 0.0571 | benign | -0.27 | Destabilizing | None | N | 0.213 | neutral | N | 0.360301733 | None | None | I |
| R/S | 0.1932 | likely_benign | 0.1763 | benign | -0.87 | Destabilizing | 0.016 | N | 0.399 | neutral | None | None | None | None | I |
| R/T | 0.0916 | likely_benign | 0.0886 | benign | -0.53 | Destabilizing | 0.031 | N | 0.409 | neutral | None | None | None | None | I |
| R/V | 0.197 | likely_benign | 0.1857 | benign | 0.04 | Stabilizing | 0.016 | N | 0.431 | neutral | None | None | None | None | I |
| R/W | 0.1486 | likely_benign | 0.1295 | benign | -0.002 | Destabilizing | 0.964 | D | 0.471 | neutral | N | 0.483846359 | None | None | I |
| R/Y | 0.2769 | likely_benign | 0.2319 | benign | 0.283 | Stabilizing | 0.001 | N | 0.304 | neutral | None | None | 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.