Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22415 | 67468;67469;67470 | chr2:178580044;178580043;178580042 | chr2:179444771;179444770;179444769 |
| N2AB | 20774 | 62545;62546;62547 | chr2:178580044;178580043;178580042 | chr2:179444771;179444770;179444769 |
| N2A | 19847 | 59764;59765;59766 | chr2:178580044;178580043;178580042 | chr2:179444771;179444770;179444769 |
| N2B | 13350 | 40273;40274;40275 | chr2:178580044;178580043;178580042 | chr2:179444771;179444770;179444769 |
| Novex-1 | 13475 | 40648;40649;40650 | chr2:178580044;178580043;178580042 | chr2:179444771;179444770;179444769 |
| Novex-2 | 13542 | 40849;40850;40851 | chr2:178580044;178580043;178580042 | chr2:179444771;179444770;179444769 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1289988673  |
-1.627 | 0.165 | N | 0.699 | 0.454 | 0.580021155531 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.53595E-04 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs1289988673 |
-1.627 | 0.165 | N | 0.699 | 0.454 | 0.580021155531 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.9478E-04 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs1289988673 |
-1.627 | 0.165 | N | 0.699 | 0.454 | 0.580021155531 | gnomAD-4.0.0 | 6.57851E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.9478E-04 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs2047350476 |
None | None | N | 0.212 | 0.094 | 0.438913950225 | 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 |
| V/I | rs2047350476 |
None | None | N | 0.212 | 0.094 | 0.438913950225 | gnomAD-4.0.0 | 6.57618E-06 | None | None | None | None | N | None | 2.41371E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.5812 | likely_pathogenic | 0.5893 | pathogenic | -1.652 | Destabilizing | 0.165 | N | 0.699 | prob.neutral | N | 0.491659675 | None | None | N |
| V/C | 0.9011 | likely_pathogenic | 0.8764 | pathogenic | -1.105 | Destabilizing | 0.981 | D | 0.787 | deleterious | None | None | None | None | N |
| V/D | 0.9829 | likely_pathogenic | 0.9823 | pathogenic | -2.046 | Highly Destabilizing | 0.818 | D | 0.825 | deleterious | None | None | None | None | N |
| V/E | 0.9562 | likely_pathogenic | 0.9563 | pathogenic | -1.795 | Destabilizing | 0.912 | D | 0.795 | deleterious | D | 0.549860008 | None | None | N |
| V/F | 0.5732 | likely_pathogenic | 0.5386 | ambiguous | -0.93 | Destabilizing | 0.69 | D | 0.787 | deleterious | None | None | None | None | N |
| V/G | 0.8323 | likely_pathogenic | 0.8324 | pathogenic | -2.207 | Highly Destabilizing | 0.773 | D | 0.779 | deleterious | D | 0.538503702 | None | None | N |
| V/H | 0.9857 | likely_pathogenic | 0.9835 | pathogenic | -1.966 | Destabilizing | 0.981 | D | 0.831 | deleterious | None | None | None | None | N |
| V/I | 0.092 | likely_benign | 0.0849 | benign | -0.102 | Destabilizing | None | N | 0.212 | neutral | N | 0.449661796 | None | None | N |
| V/K | 0.9759 | likely_pathogenic | 0.9754 | pathogenic | -1.297 | Destabilizing | 0.818 | D | 0.795 | deleterious | None | None | None | None | N |
| V/L | 0.4648 | ambiguous | 0.3951 | ambiguous | -0.102 | Destabilizing | 0.015 | N | 0.41 | neutral | N | 0.506261653 | None | None | N |
| V/M | 0.525 | ambiguous | 0.4763 | ambiguous | -0.174 | Destabilizing | 0.69 | D | 0.689 | prob.neutral | None | None | None | None | N |
| V/N | 0.961 | likely_pathogenic | 0.9607 | pathogenic | -1.699 | Destabilizing | 0.932 | D | 0.832 | deleterious | None | None | None | None | N |
| V/P | 0.953 | likely_pathogenic | 0.9425 | pathogenic | -0.592 | Destabilizing | 0.932 | D | 0.807 | deleterious | None | None | None | None | N |
| V/Q | 0.9624 | likely_pathogenic | 0.9612 | pathogenic | -1.459 | Destabilizing | 0.932 | D | 0.808 | deleterious | None | None | None | None | N |
| V/R | 0.9607 | likely_pathogenic | 0.9618 | pathogenic | -1.333 | Destabilizing | 0.818 | D | 0.829 | deleterious | None | None | None | None | N |
| V/S | 0.876 | likely_pathogenic | 0.8787 | pathogenic | -2.331 | Highly Destabilizing | 0.818 | D | 0.767 | deleterious | None | None | None | None | N |
| V/T | 0.7566 | likely_pathogenic | 0.7558 | pathogenic | -1.915 | Destabilizing | 0.388 | N | 0.715 | prob.delet. | None | None | None | None | N |
| V/W | 0.985 | likely_pathogenic | 0.9804 | pathogenic | -1.431 | Destabilizing | 0.981 | D | 0.821 | deleterious | None | None | None | None | N |
| V/Y | 0.9378 | likely_pathogenic | 0.93 | pathogenic | -0.97 | Destabilizing | 0.818 | D | 0.79 | 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.