Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26875 | 80848;80849;80850 | chr2:178565509;178565508;178565507 | chr2:179430236;179430235;179430234 |
| N2AB | 25234 | 75925;75926;75927 | chr2:178565509;178565508;178565507 | chr2:179430236;179430235;179430234 |
| N2A | 24307 | 73144;73145;73146 | chr2:178565509;178565508;178565507 | chr2:179430236;179430235;179430234 |
| N2B | 17810 | 53653;53654;53655 | chr2:178565509;178565508;178565507 | chr2:179430236;179430235;179430234 |
| Novex-1 | 17935 | 54028;54029;54030 | chr2:178565509;178565508;178565507 | chr2:179430236;179430235;179430234 |
| Novex-2 | 18002 | 54229;54230;54231 | chr2:178565509;178565508;178565507 | chr2:179430236;179430235;179430234 |
| 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/H | rs1422715847  |
0.328 | 1.0 | N | 0.875 | 0.696 | 0.446813524615 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/H | rs1422715847 |
0.328 | 1.0 | N | 0.875 | 0.696 | 0.446813524615 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/H | rs1422715847 |
0.328 | 1.0 | N | 0.875 | 0.696 | 0.446813524615 | gnomAD-4.0.0 | 2.47943E-06 | None | None | None | None | N | None | 4.00727E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60164E-05 |
| D/V | None | None | 0.999 | D | 0.799 | 0.739 | 0.770370076884 | gnomAD-4.0.0 | 1.20036E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31255E-06 | 0 | 0 |
| D/Y | rs1422715847 |
None | 1.0 | N | 0.832 | 0.738 | 0.758986609867 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/Y | rs1422715847 |
None | 1.0 | N | 0.832 | 0.738 | 0.758986609867 | gnomAD-4.0.0 | 1.23972E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69554E-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 | 0.5795 | likely_pathogenic | 0.6216 | pathogenic | -0.335 | Destabilizing | 0.999 | D | 0.731 | deleterious | N | 0.482634001 | None | None | N |
| D/C | 0.9416 | likely_pathogenic | 0.956 | pathogenic | -0.007 | Destabilizing | 0.999 | D | 0.851 | deleterious | None | None | None | None | N |
| D/E | 0.4158 | ambiguous | 0.4205 | ambiguous | -0.344 | Destabilizing | 0.978 | D | 0.515 | neutral | N | 0.512097121 | None | None | N |
| D/F | 0.936 | likely_pathogenic | 0.9409 | pathogenic | -0.333 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| D/G | 0.61 | likely_pathogenic | 0.6241 | pathogenic | -0.505 | Destabilizing | 0.999 | D | 0.796 | deleterious | N | 0.51788146 | None | None | N |
| D/H | 0.7842 | likely_pathogenic | 0.8118 | pathogenic | -0.094 | Destabilizing | 1.0 | D | 0.875 | deleterious | N | 0.503500188 | None | None | N |
| D/I | 0.8469 | likely_pathogenic | 0.877 | pathogenic | 0.06 | Stabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| D/K | 0.8928 | likely_pathogenic | 0.9067 | pathogenic | 0.307 | Stabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| D/L | 0.8454 | likely_pathogenic | 0.8729 | pathogenic | 0.06 | Stabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| D/M | 0.9393 | likely_pathogenic | 0.9473 | pathogenic | 0.196 | Stabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| D/N | 0.2529 | likely_benign | 0.2857 | benign | 0.01 | Stabilizing | 0.998 | D | 0.769 | deleterious | N | 0.496890369 | None | None | N |
| D/P | 0.8333 | likely_pathogenic | 0.8832 | pathogenic | -0.051 | Destabilizing | 0.992 | D | 0.823 | deleterious | None | None | None | None | N |
| D/Q | 0.8349 | likely_pathogenic | 0.8512 | pathogenic | 0.028 | Stabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | N |
| D/R | 0.9159 | likely_pathogenic | 0.9274 | pathogenic | 0.465 | Stabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | N |
| D/S | 0.4535 | ambiguous | 0.4922 | ambiguous | -0.082 | Destabilizing | 0.999 | D | 0.785 | deleterious | None | None | None | None | N |
| D/T | 0.7413 | likely_pathogenic | 0.7701 | pathogenic | 0.052 | Stabilizing | 0.999 | D | 0.827 | deleterious | None | None | None | None | N |
| D/V | 0.6521 | likely_pathogenic | 0.7077 | pathogenic | -0.051 | Destabilizing | 0.999 | D | 0.799 | deleterious | D | 0.529744744 | None | None | N |
| D/W | 0.9878 | likely_pathogenic | 0.9893 | pathogenic | -0.21 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | N |
| D/Y | 0.6405 | likely_pathogenic | 0.6668 | pathogenic | -0.102 | Destabilizing | 1.0 | D | 0.832 | deleterious | N | 0.519148907 | 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.