Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9516 | 28771;28772;28773 | chr2:178709773;178709772;178709771 | chr2:179574500;179574499;179574498 |
| N2AB | 9199 | 27820;27821;27822 | chr2:178709773;178709772;178709771 | chr2:179574500;179574499;179574498 |
| N2A | 8272 | 25039;25040;25041 | chr2:178709773;178709772;178709771 | chr2:179574500;179574499;179574498 |
| 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/C | rs751958797  |
-0.691 | 1.0 | None | 0.695 | 0.458 | 0.831489073666 | gnomAD-2.1.1 | 2.85E-05 | None | None | None | None | N | None | 4.13E-05 | 2.83E-05 | None | 0 | 0 | None | 1.30719E-04 | None | 0 | 1.56E-05 | 0 |
| R/C | rs751958797 |
-0.691 | 1.0 | None | 0.695 | 0.458 | 0.831489073666 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 4.79386E-04 |
| R/C | rs751958797 |
-0.691 | 1.0 | None | 0.695 | 0.458 | 0.831489073666 | gnomAD-4.0.0 | 2.72679E-05 | None | None | None | None | N | None | 0 | 1.66689E-05 | None | 0 | 0 | None | 0 | 0 | 2.45805E-05 | 1.20762E-04 | 4.80338E-05 |
| R/H | rs374156904 |
-1.431 | 0.783 | None | 0.397 | 0.24 | None | gnomAD-2.1.1 | 3.99395E-04 | None | None | None | None | N | None | 0 | 1.97997E-04 | None | 0 | 5.01741E-03 | None | 9.8E-05 | None | 0 | 0 | 5.60538E-04 |
| R/H | rs374156904 |
-1.431 | 0.783 | None | 0.397 | 0.24 | None | gnomAD-3.1.2 | 2.23449E-04 | None | None | None | None | N | None | 2.41E-05 | 1.96438E-04 | 0 | 0 | 5.39499E-03 | None | 0 | 0 | 1.47E-05 | 2.06868E-04 | 0 |
| R/H | rs374156904 |
-1.431 | 0.783 | None | 0.397 | 0.24 | None | 1000 genomes | 1.19808E-03 | None | None | None | None | N | None | 0 | 0 | None | None | 6E-03 | 0 | None | None | None | 0 | None |
| R/H | rs374156904 |
-1.431 | 0.783 | None | 0.397 | 0.24 | None | gnomAD-4.0.0 | 2.54062E-04 | None | None | None | None | N | None | 2.66581E-05 | 1.83297E-04 | None | 0 | 7.30968E-03 | None | 0 | 0 | 1.35616E-05 | 8.7831E-05 | 7.20184E-04 |
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 | 0.6287 | likely_pathogenic | 0.6235 | pathogenic | -1.021 | Destabilizing | 0.996 | D | 0.607 | neutral | None | None | None | None | N |
| R/C | 0.2624 | likely_benign | 0.2507 | benign | -0.967 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| R/D | 0.8913 | likely_pathogenic | 0.8804 | pathogenic | -0.223 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | N |
| R/E | 0.5996 | likely_pathogenic | 0.5924 | pathogenic | -0.114 | Destabilizing | 0.992 | D | 0.565 | neutral | None | None | None | None | N |
| R/F | 0.6736 | likely_pathogenic | 0.6491 | pathogenic | -0.957 | Destabilizing | 0.999 | D | 0.721 | prob.delet. | None | None | None | None | N |
| R/G | 0.5817 | likely_pathogenic | 0.5575 | ambiguous | -1.315 | Destabilizing | 0.998 | D | 0.653 | neutral | None | None | None | None | N |
| R/H | 0.1602 | likely_benign | 0.1291 | benign | -1.527 | Destabilizing | 0.783 | D | 0.397 | neutral | None | None | None | None | N |
| R/I | 0.3507 | ambiguous | 0.3951 | ambiguous | -0.231 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| R/K | 0.1561 | likely_benign | 0.1547 | benign | -1.078 | Destabilizing | 0.99 | D | 0.513 | neutral | None | None | None | None | N |
| R/L | 0.3948 | ambiguous | 0.3903 | ambiguous | -0.231 | Destabilizing | 0.999 | D | 0.659 | neutral | None | None | None | None | N |
| R/M | 0.3896 | ambiguous | 0.4217 | ambiguous | -0.431 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| R/N | 0.7653 | likely_pathogenic | 0.7421 | pathogenic | -0.458 | Destabilizing | 0.992 | D | 0.619 | neutral | None | None | None | None | N |
| R/P | 0.9649 | likely_pathogenic | 0.9653 | pathogenic | -0.475 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| R/Q | 0.1553 | likely_benign | 0.1451 | benign | -0.7 | Destabilizing | 0.999 | D | 0.658 | neutral | None | None | None | None | N |
| R/S | 0.7083 | likely_pathogenic | 0.6958 | pathogenic | -1.287 | Destabilizing | 0.998 | D | 0.672 | neutral | None | None | None | None | N |
| R/T | 0.4006 | ambiguous | 0.4187 | ambiguous | -1.004 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| R/V | 0.4583 | ambiguous | 0.4831 | ambiguous | -0.475 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| R/W | 0.3046 | likely_benign | 0.2757 | benign | -0.574 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | N |
| R/Y | 0.5614 | ambiguous | 0.5131 | ambiguous | -0.283 | Destabilizing | 0.998 | D | 0.72 | prob.delet. | None | None | 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.