Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35899 | 107920;107921;107922 | chr2:178527293;178527292;178527291 | chr2:179392020;179392019;179392018 |
| N2AB | 34258 | 102997;102998;102999 | chr2:178527293;178527292;178527291 | chr2:179392020;179392019;179392018 |
| N2A | 33331 | 100216;100217;100218 | chr2:178527293;178527292;178527291 | chr2:179392020;179392019;179392018 |
| N2B | 26834 | 80725;80726;80727 | chr2:178527293;178527292;178527291 | chr2:179392020;179392019;179392018 |
| Novex-1 | 26959 | 81100;81101;81102 | chr2:178527293;178527292;178527291 | chr2:179392020;179392019;179392018 |
| Novex-2 | 27026 | 81301;81302;81303 | chr2:178527293;178527292;178527291 | chr2:179392020;179392019;179392018 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs372276487  |
-2.598 | 1.0 | D | 0.794 | 0.688 | None | gnomAD-2.1.1 | 3.01E-05 | None | None | None | -0.311(OBSL1) -0.261(OBSCN) | N | None | 2.09661E-04 | 0 | None | 0 | 0 | None | 3.64E-05 | None | 0 | 1.63E-05 | 0 |
| I/T | rs372276487 |
-2.598 | 1.0 | D | 0.794 | 0.688 | None | gnomAD-3.1.2 | 6.57E-05 | None | None | None | -0.311(OBSL1) -0.261(OBSCN) | N | None | 1.93032E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/T | rs372276487 |
-2.598 | 1.0 | D | 0.794 | 0.688 | None | gnomAD-4.0.0 | 1.94414E-05 | None | None | None | -0.311(OBSL1) -0.261(OBSCN) | N | None | 1.75794E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 8.54964E-06 | 7.93309E-05 | 1.62639E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9426 | likely_pathogenic | 0.9428 | pathogenic | -2.443 | Highly Destabilizing | 0.999 | D | 0.669 | neutral | None | None | None | 0.361(OBSL1) -0.62(OBSCN) | N |
| I/C | 0.9928 | likely_pathogenic | 0.9937 | pathogenic | -1.728 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | -1.065(OBSL1) 0.008(OBSCN) | N |
| I/D | 0.9974 | likely_pathogenic | 0.9973 | pathogenic | -2.316 | Highly Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | -0.825(OBSL1) -0.055(OBSCN) | N |
| I/E | 0.9892 | likely_pathogenic | 0.9872 | pathogenic | -2.206 | Highly Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | -0.965(OBSL1) -0.112(OBSCN) | N |
| I/F | 0.7937 | likely_pathogenic | 0.7911 | pathogenic | -1.556 | Destabilizing | 1.0 | D | 0.791 | deleterious | N | 0.493708935 | None | 0.026(OBSL1) -0.046(OBSCN) | N |
| I/G | 0.9933 | likely_pathogenic | 0.993 | pathogenic | -2.901 | Highly Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | 0.419(OBSL1) -0.605(OBSCN) | N |
| I/H | 0.9951 | likely_pathogenic | 0.9947 | pathogenic | -2.132 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | 0.088(OBSL1) 0.257(OBSCN) | N |
| I/K | 0.9712 | likely_pathogenic | 0.965 | pathogenic | -1.878 | Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | -0.892(OBSL1) -0.391(OBSCN) | N |
| I/L | 0.5074 | ambiguous | 0.4983 | ambiguous | -1.175 | Destabilizing | 0.993 | D | 0.526 | neutral | N | 0.491078515 | None | 0.087(OBSL1) -0.663(OBSCN) | N |
| I/M | 0.365 | ambiguous | 0.3578 | ambiguous | -0.997 | Destabilizing | 1.0 | D | 0.767 | deleterious | N | 0.512540586 | None | -0.451(OBSL1) -0.209(OBSCN) | N |
| I/N | 0.9702 | likely_pathogenic | 0.9674 | pathogenic | -1.885 | Destabilizing | 1.0 | D | 0.871 | deleterious | D | 0.545737356 | None | -0.31(OBSL1) -0.451(OBSCN) | N |
| I/P | 0.9876 | likely_pathogenic | 0.9867 | pathogenic | -1.572 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | 0.193(OBSL1) -0.649(OBSCN) | N |
| I/Q | 0.9857 | likely_pathogenic | 0.9833 | pathogenic | -1.945 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | -0.485(OBSL1) -0.304(OBSCN) | N |
| I/R | 0.9637 | likely_pathogenic | 0.9571 | pathogenic | -1.333 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | -0.77(OBSL1) -0.497(OBSCN) | N |
| I/S | 0.9708 | likely_pathogenic | 0.9688 | pathogenic | -2.592 | Highly Destabilizing | 1.0 | D | 0.837 | deleterious | D | 0.522771256 | None | -0.173(OBSL1) -0.217(OBSCN) | N |
| I/T | 0.9082 | likely_pathogenic | 0.9041 | pathogenic | -2.35 | Highly Destabilizing | 1.0 | D | 0.794 | deleterious | D | 0.522517766 | None | -0.311(OBSL1) -0.261(OBSCN) | N |
| I/V | 0.2717 | likely_benign | 0.274 | benign | -1.572 | Destabilizing | 0.993 | D | 0.469 | neutral | D | 0.528173799 | None | 0.193(OBSL1) -0.649(OBSCN) | N |
| I/W | 0.9892 | likely_pathogenic | 0.9893 | pathogenic | -1.766 | Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | -0.52(OBSL1) -0.009(OBSCN) | N |
| I/Y | 0.9701 | likely_pathogenic | 0.9698 | pathogenic | -1.555 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | 0.008(OBSL1) -0.104(OBSCN) | 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.