Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22368 | 67327;67328;67329 | chr2:178580185;178580184;178580183 | chr2:179444912;179444911;179444910 |
| N2AB | 20727 | 62404;62405;62406 | chr2:178580185;178580184;178580183 | chr2:179444912;179444911;179444910 |
| N2A | 19800 | 59623;59624;59625 | chr2:178580185;178580184;178580183 | chr2:179444912;179444911;179444910 |
| N2B | 13303 | 40132;40133;40134 | chr2:178580185;178580184;178580183 | chr2:179444912;179444911;179444910 |
| Novex-1 | 13428 | 40507;40508;40509 | chr2:178580185;178580184;178580183 | chr2:179444912;179444911;179444910 |
| Novex-2 | 13495 | 40708;40709;40710 | chr2:178580185;178580184;178580183 | chr2:179444912;179444911;179444910 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | rs879076636  |
None | 0.892 | N | 0.504 | 0.203 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93798E-04 | None | 0 | 0 | 0 | 0 | 0 |
| K/E | rs879076636 |
None | 0.892 | N | 0.504 | 0.203 | None | gnomAD-4.0.0 | 1.23981E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.23604E-05 | None | 0 | 0 | 8.47838E-07 | 0 | 0 |
| K/N | rs727503577 |
0.332 | 0.967 | N | 0.661 | 0.19 | 0.208816687407 | gnomAD-2.1.1 | 4.44E-05 | None | None | None | None | N | None | 0 | 0 | None | 9.97009E-04 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| K/N | rs727503577 |
0.332 | 0.967 | N | 0.661 | 0.19 | 0.208816687407 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 1.44009E-03 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| K/N | rs727503577 |
0.332 | 0.967 | N | 0.661 | 0.19 | 0.208816687407 | gnomAD-4.0.0 | 3.40964E-05 | None | None | None | None | N | None | 0 | 0 | None | 1.28457E-03 | 0 | None | 0 | 1.64799E-04 | 1.01739E-05 | 0 | 6.40882E-05 |
| K/Q | None | None | 0.967 | N | 0.671 | 0.235 | 0.222439326576 | gnomAD-4.0.0 | 6.84488E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87406E-05 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.4946 | ambiguous | 0.3913 | ambiguous | -0.315 | Destabilizing | 0.916 | D | 0.557 | neutral | None | None | None | None | N |
| K/C | 0.8212 | likely_pathogenic | 0.7319 | pathogenic | -0.484 | Destabilizing | 0.999 | D | 0.801 | deleterious | None | None | None | None | N |
| K/D | 0.847 | likely_pathogenic | 0.7762 | pathogenic | -0.471 | Destabilizing | 0.987 | D | 0.696 | prob.neutral | None | None | None | None | N |
| K/E | 0.3678 | ambiguous | 0.2917 | benign | -0.472 | Destabilizing | 0.892 | D | 0.504 | neutral | N | 0.518420087 | None | None | N |
| K/F | 0.941 | likely_pathogenic | 0.9006 | pathogenic | -0.79 | Destabilizing | 0.999 | D | 0.767 | deleterious | None | None | None | None | N |
| K/G | 0.6011 | likely_pathogenic | 0.4936 | ambiguous | -0.516 | Destabilizing | 0.975 | D | 0.63 | neutral | None | None | None | None | N |
| K/H | 0.5989 | likely_pathogenic | 0.4988 | ambiguous | -1.065 | Destabilizing | 0.997 | D | 0.671 | neutral | None | None | None | None | N |
| K/I | 0.6328 | likely_pathogenic | 0.5329 | ambiguous | 0.138 | Stabilizing | 0.983 | D | 0.782 | deleterious | N | 0.516073218 | None | None | N |
| K/L | 0.6364 | likely_pathogenic | 0.5267 | ambiguous | 0.138 | Stabilizing | 0.975 | D | 0.63 | neutral | None | None | None | None | N |
| K/M | 0.4659 | ambiguous | 0.3783 | ambiguous | 0.366 | Stabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | N |
| K/N | 0.722 | likely_pathogenic | 0.6513 | pathogenic | -0.075 | Destabilizing | 0.967 | D | 0.661 | neutral | N | 0.465986734 | None | None | N |
| K/P | 0.7824 | likely_pathogenic | 0.6643 | pathogenic | 0.014 | Stabilizing | 0.996 | D | 0.693 | prob.neutral | None | None | None | None | N |
| K/Q | 0.2599 | likely_benign | 0.2134 | benign | -0.46 | Destabilizing | 0.967 | D | 0.671 | neutral | N | 0.480825759 | None | None | N |
| K/R | 0.0832 | likely_benign | 0.0779 | benign | -0.091 | Destabilizing | 0.025 | N | 0.191 | neutral | N | 0.471919793 | None | None | N |
| K/S | 0.6123 | likely_pathogenic | 0.5168 | ambiguous | -0.598 | Destabilizing | 0.916 | D | 0.591 | neutral | None | None | None | None | N |
| K/T | 0.3846 | ambiguous | 0.2886 | benign | -0.455 | Destabilizing | 0.967 | D | 0.651 | neutral | N | 0.47073322 | None | None | N |
| K/V | 0.5494 | ambiguous | 0.4426 | ambiguous | 0.014 | Stabilizing | 0.987 | D | 0.715 | prob.delet. | None | None | None | None | N |
| K/W | 0.9178 | likely_pathogenic | 0.8649 | pathogenic | -0.71 | Destabilizing | 0.999 | D | 0.802 | deleterious | None | None | None | None | N |
| K/Y | 0.8732 | likely_pathogenic | 0.8101 | pathogenic | -0.285 | Destabilizing | 0.996 | D | 0.742 | deleterious | 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.