Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21633 | 65122;65123;65124 | chr2:178584744;178584743;178584742 | chr2:179449471;179449470;179449469 |
| N2AB | 19992 | 60199;60200;60201 | chr2:178584744;178584743;178584742 | chr2:179449471;179449470;179449469 |
| N2A | 19065 | 57418;57419;57420 | chr2:178584744;178584743;178584742 | chr2:179449471;179449470;179449469 |
| N2B | 12568 | 37927;37928;37929 | chr2:178584744;178584743;178584742 | chr2:179449471;179449470;179449469 |
| Novex-1 | 12693 | 38302;38303;38304 | chr2:178584744;178584743;178584742 | chr2:179449471;179449470;179449469 |
| Novex-2 | 12760 | 38503;38504;38505 | chr2:178584744;178584743;178584742 | chr2:179449471;179449470;179449469 |
| 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/Q | rs141965360  |
-1.041 | 1.0 | N | 0.796 | 0.426 | None | gnomAD-2.1.1 | 1.07196E-04 | None | None | None | None | N | None | 3.72055E-04 | 1.69702E-04 | None | 0 | 0 | None | 0 | None | 0 | 1.17406E-04 | 0 |
| R/Q | rs141965360 |
-1.041 | 1.0 | N | 0.796 | 0.426 | None | gnomAD-3.1.2 | 1.51272E-04 | None | None | None | None | N | None | 2.65598E-04 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.61803E-04 | 0 | 0 |
| R/Q | rs141965360 |
-1.041 | 1.0 | N | 0.796 | 0.426 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs141965360 |
-1.041 | 1.0 | N | 0.796 | 0.426 | None | gnomAD-4.0.0 | 6.25987E-05 | None | None | None | None | N | None | 3.06732E-04 | 1.66717E-04 | None | 0 | 0 | None | 0 | 0 | 5.59524E-05 | 0 | 3.20215E-05 |
| R/W | rs749576292 |
-0.597 | 1.0 | D | 0.78 | 0.501 | 0.728441653118 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.83E-06 | 0 |
| R/W | rs749576292 |
-0.597 | 1.0 | D | 0.78 | 0.501 | 0.728441653118 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/W | rs749576292 |
-0.597 | 1.0 | D | 0.78 | 0.501 | 0.728441653118 | gnomAD-4.0.0 | 6.19837E-06 | None | None | None | None | N | None | 1.33586E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 7.62981E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9611 | likely_pathogenic | 0.9682 | pathogenic | -1.965 | Destabilizing | 0.999 | D | 0.607 | neutral | None | None | None | None | N |
| R/C | 0.4868 | ambiguous | 0.5264 | ambiguous | -1.794 | Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| R/D | 0.9967 | likely_pathogenic | 0.9977 | pathogenic | -1.127 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| R/E | 0.9486 | likely_pathogenic | 0.958 | pathogenic | -0.909 | Destabilizing | 0.999 | D | 0.691 | prob.neutral | None | None | None | None | N |
| R/F | 0.9862 | likely_pathogenic | 0.9886 | pathogenic | -1.04 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| R/G | 0.9623 | likely_pathogenic | 0.971 | pathogenic | -2.285 | Highly Destabilizing | 1.0 | D | 0.724 | prob.delet. | D | 0.548717464 | None | None | N |
| R/H | 0.4358 | ambiguous | 0.4995 | ambiguous | -2.144 | Highly Destabilizing | 1.0 | D | 0.822 | deleterious | None | None | None | None | N |
| R/I | 0.9272 | likely_pathogenic | 0.9371 | pathogenic | -1.026 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| R/K | 0.4147 | ambiguous | 0.4372 | ambiguous | -1.256 | Destabilizing | 0.998 | D | 0.644 | neutral | None | None | None | None | N |
| R/L | 0.8913 | likely_pathogenic | 0.9088 | pathogenic | -1.026 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | N | 0.51819372 | None | None | N |
| R/M | 0.9226 | likely_pathogenic | 0.9369 | pathogenic | -1.576 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| R/N | 0.9851 | likely_pathogenic | 0.9882 | pathogenic | -1.373 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| R/P | 0.9991 | likely_pathogenic | 0.9994 | pathogenic | -1.33 | Destabilizing | 1.0 | D | 0.81 | deleterious | D | 0.560580749 | None | None | N |
| R/Q | 0.3437 | ambiguous | 0.3815 | ambiguous | -1.126 | Destabilizing | 1.0 | D | 0.796 | deleterious | N | 0.507189355 | None | None | N |
| R/S | 0.9709 | likely_pathogenic | 0.9767 | pathogenic | -2.126 | Highly Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| R/T | 0.941 | likely_pathogenic | 0.9556 | pathogenic | -1.712 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| R/V | 0.9334 | likely_pathogenic | 0.9388 | pathogenic | -1.33 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| R/W | 0.8229 | likely_pathogenic | 0.8729 | pathogenic | -0.661 | Destabilizing | 1.0 | D | 0.78 | deleterious | D | 0.537614648 | None | None | N |
| R/Y | 0.9532 | likely_pathogenic | 0.9635 | pathogenic | -0.55 | Destabilizing | 1.0 | D | 0.837 | 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.