Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26403 | 79432;79433;79434 | chr2:178566925;178566924;178566923 | chr2:179431652;179431651;179431650 |
| N2AB | 24762 | 74509;74510;74511 | chr2:178566925;178566924;178566923 | chr2:179431652;179431651;179431650 |
| N2A | 23835 | 71728;71729;71730 | chr2:178566925;178566924;178566923 | chr2:179431652;179431651;179431650 |
| N2B | 17338 | 52237;52238;52239 | chr2:178566925;178566924;178566923 | chr2:179431652;179431651;179431650 |
| Novex-1 | 17463 | 52612;52613;52614 | chr2:178566925;178566924;178566923 | chr2:179431652;179431651;179431650 |
| Novex-2 | 17530 | 52813;52814;52815 | chr2:178566925;178566924;178566923 | chr2:179431652;179431651;179431650 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs1706091561  |
None | 0.985 | N | 0.641 | 0.417 | 0.50857664894 | gnomAD-4.0.0 | 6.84282E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99539E-07 | 0 | 0 |
| M/K | rs1469438235 |
-0.272 | 0.994 | N | 0.795 | 0.65 | 0.681219007559 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/K | rs1469438235 |
-0.272 | 0.994 | N | 0.795 | 0.65 | 0.681219007559 | gnomAD-4.0.0 | 4.77483E-06 | None | None | None | None | N | None | 0 | 6.86091E-05 | None | 0 | 0 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.8647 | likely_pathogenic | 0.834 | pathogenic | -2.024 | Highly Destabilizing | 0.989 | D | 0.697 | prob.neutral | None | None | None | None | N |
| M/C | 0.9002 | likely_pathogenic | 0.9038 | pathogenic | -2.515 | Highly Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | N |
| M/D | 0.9997 | likely_pathogenic | 0.9996 | pathogenic | -2.003 | Highly Destabilizing | 0.999 | D | 0.825 | deleterious | None | None | None | None | N |
| M/E | 0.9972 | likely_pathogenic | 0.9957 | pathogenic | -1.743 | Destabilizing | 0.999 | D | 0.796 | deleterious | None | None | None | None | N |
| M/F | 0.8932 | likely_pathogenic | 0.8837 | pathogenic | -0.644 | Destabilizing | 0.999 | D | 0.723 | prob.delet. | None | None | None | None | N |
| M/G | 0.9907 | likely_pathogenic | 0.9888 | pathogenic | -2.53 | Highly Destabilizing | 0.995 | D | 0.768 | deleterious | None | None | None | None | N |
| M/H | 0.9981 | likely_pathogenic | 0.9974 | pathogenic | -2.337 | Highly Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| M/I | 0.8609 | likely_pathogenic | 0.7779 | pathogenic | -0.563 | Destabilizing | 0.985 | D | 0.641 | neutral | N | 0.419584031 | None | None | N |
| M/K | 0.994 | likely_pathogenic | 0.9907 | pathogenic | -1.193 | Destabilizing | 0.994 | D | 0.795 | deleterious | N | 0.510148189 | None | None | N |
| M/L | 0.5764 | likely_pathogenic | 0.5132 | ambiguous | -0.563 | Destabilizing | 0.927 | D | 0.434 | neutral | N | 0.457174053 | None | None | N |
| M/N | 0.9968 | likely_pathogenic | 0.9956 | pathogenic | -1.689 | Destabilizing | 0.999 | D | 0.805 | deleterious | None | None | None | None | N |
| M/P | 0.9997 | likely_pathogenic | 0.9996 | pathogenic | -1.032 | Destabilizing | 0.999 | D | 0.805 | deleterious | None | None | None | None | N |
| M/Q | 0.969 | likely_pathogenic | 0.9636 | pathogenic | -1.296 | Destabilizing | 0.999 | D | 0.737 | prob.delet. | None | None | None | None | N |
| M/R | 0.9933 | likely_pathogenic | 0.99 | pathogenic | -1.51 | Destabilizing | 0.998 | D | 0.83 | deleterious | N | 0.498627299 | None | None | N |
| M/S | 0.9703 | likely_pathogenic | 0.9623 | pathogenic | -2.234 | Highly Destabilizing | 0.995 | D | 0.767 | deleterious | None | None | None | None | N |
| M/T | 0.9656 | likely_pathogenic | 0.9483 | pathogenic | -1.829 | Destabilizing | 0.994 | D | 0.79 | deleterious | N | 0.483143164 | None | None | N |
| M/V | 0.3195 | likely_benign | 0.2471 | benign | -1.032 | Destabilizing | 0.985 | D | 0.535 | neutral | N | 0.39789925 | None | None | N |
| M/W | 0.9977 | likely_pathogenic | 0.9973 | pathogenic | -0.994 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| M/Y | 0.9949 | likely_pathogenic | 0.994 | pathogenic | -0.928 | Destabilizing | 0.999 | D | 0.829 | 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.