Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20001 | 60226;60227;60228 | chr2:178591818;178591817;178591816 | chr2:179456545;179456544;179456543 |
| N2AB | 18360 | 55303;55304;55305 | chr2:178591818;178591817;178591816 | chr2:179456545;179456544;179456543 |
| N2A | 17433 | 52522;52523;52524 | chr2:178591818;178591817;178591816 | chr2:179456545;179456544;179456543 |
| N2B | 10936 | 33031;33032;33033 | chr2:178591818;178591817;178591816 | chr2:179456545;179456544;179456543 |
| Novex-1 | 11061 | 33406;33407;33408 | chr2:178591818;178591817;178591816 | chr2:179456545;179456544;179456543 |
| Novex-2 | 11128 | 33607;33608;33609 | chr2:178591818;178591817;178591816 | chr2:179456545;179456544;179456543 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs727505345  |
-0.495 | 1.0 | D | 0.911 | 0.543 | None | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 1.55167E-04 | None | 0 | None | 0 | 2.35E-05 | 0 |
| P/L | rs727505345 |
-0.495 | 1.0 | D | 0.911 | 0.543 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 1.94401E-04 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| P/L | rs727505345 |
-0.495 | 1.0 | D | 0.911 | 0.543 | None | gnomAD-4.0.0 | 1.5498E-05 | None | None | None | None | N | None | 5.34231E-05 | 0 | None | 0 | 2.23764E-05 | None | 1.56289E-05 | 0 | 1.52598E-05 | 0 | 1.60164E-05 |
| P/T | None | None | 1.0 | D | 0.871 | 0.546 | 0.6216725 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.8949 | likely_pathogenic | 0.92 | pathogenic | -2.033 | Highly Destabilizing | 1.0 | D | 0.84 | deleterious | D | 0.5653455 | None | None | N |
| P/C | 0.9905 | likely_pathogenic | 0.9944 | pathogenic | -1.358 | Destabilizing | 1.0 | D | 0.864 | deleterious | None | None | None | None | N |
| P/D | 0.9978 | likely_pathogenic | 0.9984 | pathogenic | -2.579 | Highly Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| P/E | 0.9961 | likely_pathogenic | 0.9971 | pathogenic | -2.482 | Highly Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| P/F | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -1.405 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| P/G | 0.9851 | likely_pathogenic | 0.9889 | pathogenic | -2.461 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| P/H | 0.9947 | likely_pathogenic | 0.9965 | pathogenic | -2.216 | Highly Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| P/I | 0.9952 | likely_pathogenic | 0.9968 | pathogenic | -0.887 | Destabilizing | 1.0 | D | 0.892 | deleterious | None | None | None | None | N |
| P/K | 0.9978 | likely_pathogenic | 0.9984 | pathogenic | -1.852 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| P/L | 0.9801 | likely_pathogenic | 0.9856 | pathogenic | -0.887 | Destabilizing | 1.0 | D | 0.911 | deleterious | D | 0.59930223 | None | None | N |
| P/M | 0.9947 | likely_pathogenic | 0.9965 | pathogenic | -0.637 | Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | N |
| P/N | 0.9971 | likely_pathogenic | 0.998 | pathogenic | -1.817 | Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | None | N |
| P/Q | 0.9946 | likely_pathogenic | 0.9963 | pathogenic | -1.863 | Destabilizing | 1.0 | D | 0.857 | deleterious | D | 0.6056511 | None | None | N |
| P/R | 0.993 | likely_pathogenic | 0.995 | pathogenic | -1.411 | Destabilizing | 1.0 | D | 0.895 | deleterious | D | 0.5799112 | None | None | N |
| P/S | 0.9804 | likely_pathogenic | 0.9864 | pathogenic | -2.314 | Highly Destabilizing | 1.0 | D | 0.868 | deleterious | D | 0.5593699 | None | None | N |
| P/T | 0.9714 | likely_pathogenic | 0.9796 | pathogenic | -2.106 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | D | 0.58899593 | None | None | N |
| P/V | 0.984 | likely_pathogenic | 0.9891 | pathogenic | -1.239 | Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| P/W | 0.9994 | likely_pathogenic | 0.9996 | pathogenic | -1.838 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| P/Y | 0.9992 | likely_pathogenic | 0.9994 | pathogenic | -1.525 | Destabilizing | 1.0 | D | 0.901 | 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.