Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4900 | 14923;14924;14925 | chr2:178735748;178735747;178735746 | chr2:179600475;179600474;179600473 |
| N2AB | 4583 | 13972;13973;13974 | chr2:178735748;178735747;178735746 | chr2:179600475;179600474;179600473 |
| N2A | 3656 | 11191;11192;11193 | chr2:178735748;178735747;178735746 | chr2:179600475;179600474;179600473 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | rs72648923  |
-0.637 | 1.0 | N | 0.671 | 0.34 | 0.629195211289 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| A/P | rs72648923 |
-0.637 | 1.0 | N | 0.671 | 0.34 | 0.629195211289 | gnomAD-4.0.0 | 1.36849E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79893E-06 | 0 | 0 |
| A/T | None | -0.422 | 0.999 | N | 0.675 | 0.293 | None | gnomAD-2.1.1 | 3.78068E-03 | None | None | None | None | I | None | 1.23998E-04 | 4.24761E-04 | None | 1.83752E-03 | 0 | None | 5.88466E-04 | None | 1.53298E-02 | 4.66851E-03 | 3.23579E-03 |
| A/T | None | -0.422 | 0.999 | N | 0.675 | 0.293 | None | gnomAD-3.1.2 | 3.20669E-03 | None | None | None | None | I | None | 9.65E-05 | 1.96464E-04 | 0 | 2.01729E-03 | 0 | None | 1.60226E-02 | 3.16456E-03 | 4.30667E-03 | 1.24121E-03 | 1.91205E-03 |
| A/T | None | -0.422 | 0.999 | N | 0.675 | 0.293 | None | 1000 genomes | 1.79712E-03 | None | None | None | None | I | None | 0 | 1.4E-03 | None | None | 0 | 7E-03 | None | None | None | 1E-03 | None |
| A/T | None | -0.422 | 0.999 | N | 0.675 | 0.293 | None | gnomAD-4.0.0 | 2.54745E-03 | None | None | None | None | I | None | 7.99446E-05 | 4.33333E-04 | None | 1.25E-03 | 0 | None | 1.55679E-02 | 4.9505E-04 | 2.41906E-03 | 6.8069E-04 | 2.03285E-03 |
| A/V | rs771948633 |
-0.139 | 0.884 | N | 0.37 | 0.284 | None | gnomAD-2.1.1 | 8.93E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.23431E-03 | None | 0 | None | 0 | 0 | 1.40647E-04 |
| A/V | rs771948633 |
-0.139 | 0.884 | N | 0.37 | 0.284 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.92604E-04 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs771948633 |
-0.139 | 0.884 | N | 0.37 | 0.284 | None | gnomAD-4.0.0 | 1.36339E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 4.01481E-04 | None | 0 | 0 | 0 | 2.19582E-05 | 3.20266E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5932 | likely_pathogenic | 0.6362 | pathogenic | -0.776 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | I |
| A/D | 0.3984 | ambiguous | 0.4193 | ambiguous | -0.513 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | N | 0.505088798 | None | None | I |
| A/E | 0.3398 | likely_benign | 0.3668 | ambiguous | -0.646 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | None | None | None | None | I |
| A/F | 0.3825 | ambiguous | 0.4147 | ambiguous | -1.0 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | I |
| A/G | 0.1652 | likely_benign | 0.1888 | benign | -0.681 | Destabilizing | 0.999 | D | 0.629 | neutral | N | 0.506884106 | None | None | I |
| A/H | 0.5696 | likely_pathogenic | 0.6071 | pathogenic | -0.693 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| A/I | 0.2453 | likely_benign | 0.2728 | benign | -0.461 | Destabilizing | 0.994 | D | 0.623 | neutral | None | None | None | None | I |
| A/K | 0.5401 | ambiguous | 0.5721 | pathogenic | -0.809 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | I |
| A/L | 0.2049 | likely_benign | 0.217 | benign | -0.461 | Destabilizing | 0.994 | D | 0.555 | neutral | None | None | None | None | I |
| A/M | 0.2701 | likely_benign | 0.2958 | benign | -0.393 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | I |
| A/N | 0.309 | likely_benign | 0.3365 | benign | -0.435 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | I |
| A/P | 0.1472 | likely_benign | 0.1627 | benign | -0.46 | Destabilizing | 1.0 | D | 0.671 | neutral | N | 0.475913339 | None | None | I |
| A/Q | 0.4037 | ambiguous | 0.4368 | ambiguous | -0.723 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| A/R | 0.4931 | ambiguous | 0.5146 | ambiguous | -0.348 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | I |
| A/S | 0.1055 | likely_benign | 0.1097 | benign | -0.717 | Destabilizing | 0.999 | D | 0.63 | neutral | N | 0.497376738 | None | None | I |
| A/T | 0.1039 | likely_benign | 0.1097 | benign | -0.77 | Destabilizing | 0.999 | D | 0.675 | prob.neutral | N | 0.484252716 | None | None | I |
| A/V | 0.1257 | likely_benign | 0.1363 | benign | -0.46 | Destabilizing | 0.884 | D | 0.37 | neutral | N | 0.458513246 | None | None | I |
| A/W | 0.7894 | likely_pathogenic | 0.8281 | pathogenic | -1.141 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| A/Y | 0.5483 | ambiguous | 0.5958 | pathogenic | -0.8 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | 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.