Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21592 | 64999;65000;65001 | chr2:178584867;178584866;178584865 | chr2:179449594;179449593;179449592 |
| N2AB | 19951 | 60076;60077;60078 | chr2:178584867;178584866;178584865 | chr2:179449594;179449593;179449592 |
| N2A | 19024 | 57295;57296;57297 | chr2:178584867;178584866;178584865 | chr2:179449594;179449593;179449592 |
| N2B | 12527 | 37804;37805;37806 | chr2:178584867;178584866;178584865 | chr2:179449594;179449593;179449592 |
| Novex-1 | 12652 | 38179;38180;38181 | chr2:178584867;178584866;178584865 | chr2:179449594;179449593;179449592 |
| Novex-2 | 12719 | 38380;38381;38382 | chr2:178584867;178584866;178584865 | chr2:179449594;179449593;179449592 |
| 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/F | rs727503581  |
-1.891 | 0.942 | D | 0.719 | 0.409 | 0.681350956159 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| I/F | rs727503581 |
-1.891 | 0.942 | D | 0.719 | 0.409 | 0.681350956159 | gnomAD-4.0.0 | 6.84358E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99619E-07 | 0 | 0 |
| I/N | None | None | 0.99 | D | 0.839 | 0.534 | 0.891053409257 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.75482E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs727503581 |
-1.625 | 0.006 | N | 0.233 | 0.161 | 0.448696893172 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.30719E-04 | None | 0 | 0 | 0 |
| I/V | rs727503581 |
-1.625 | 0.006 | N | 0.233 | 0.161 | 0.448696893172 | gnomAD-4.0.0 | 8.21229E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.3914E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9863 | likely_pathogenic | 0.9854 | pathogenic | -2.403 | Highly Destabilizing | 0.754 | D | 0.655 | neutral | None | None | None | None | I |
| I/C | 0.9826 | likely_pathogenic | 0.9811 | pathogenic | -1.676 | Destabilizing | 0.994 | D | 0.733 | prob.delet. | None | None | None | None | I |
| I/D | 0.999 | likely_pathogenic | 0.999 | pathogenic | -2.583 | Highly Destabilizing | 0.993 | D | 0.844 | deleterious | None | None | None | None | I |
| I/E | 0.997 | likely_pathogenic | 0.9967 | pathogenic | -2.515 | Highly Destabilizing | 0.978 | D | 0.838 | deleterious | None | None | None | None | I |
| I/F | 0.9515 | likely_pathogenic | 0.9526 | pathogenic | -1.805 | Destabilizing | 0.942 | D | 0.719 | prob.delet. | D | 0.545274424 | None | None | I |
| I/G | 0.9981 | likely_pathogenic | 0.998 | pathogenic | -2.813 | Highly Destabilizing | 0.978 | D | 0.836 | deleterious | None | None | None | None | I |
| I/H | 0.9969 | likely_pathogenic | 0.997 | pathogenic | -2.142 | Highly Destabilizing | 0.998 | D | 0.801 | deleterious | None | None | None | None | I |
| I/K | 0.9898 | likely_pathogenic | 0.989 | pathogenic | -1.794 | Destabilizing | 0.978 | D | 0.835 | deleterious | None | None | None | None | I |
| I/L | 0.5552 | ambiguous | 0.5906 | pathogenic | -1.281 | Destabilizing | 0.294 | N | 0.424 | neutral | N | 0.489960927 | None | None | I |
| I/M | 0.6868 | likely_pathogenic | 0.6777 | pathogenic | -0.957 | Destabilizing | 0.942 | D | 0.693 | prob.neutral | D | 0.547809319 | None | None | I |
| I/N | 0.9797 | likely_pathogenic | 0.9775 | pathogenic | -1.791 | Destabilizing | 0.99 | D | 0.839 | deleterious | D | 0.537466972 | None | None | I |
| I/P | 0.9818 | likely_pathogenic | 0.9789 | pathogenic | -1.63 | Destabilizing | 0.993 | D | 0.842 | deleterious | None | None | None | None | I |
| I/Q | 0.9951 | likely_pathogenic | 0.9945 | pathogenic | -1.926 | Destabilizing | 0.993 | D | 0.833 | deleterious | None | None | None | None | I |
| I/R | 0.9875 | likely_pathogenic | 0.9865 | pathogenic | -1.185 | Destabilizing | 0.978 | D | 0.839 | deleterious | None | None | None | None | I |
| I/S | 0.9878 | likely_pathogenic | 0.9868 | pathogenic | -2.406 | Highly Destabilizing | 0.942 | D | 0.815 | deleterious | D | 0.559583698 | None | None | I |
| I/T | 0.9622 | likely_pathogenic | 0.9527 | pathogenic | -2.214 | Highly Destabilizing | 0.822 | D | 0.763 | deleterious | D | 0.525350198 | None | None | I |
| I/V | 0.1416 | likely_benign | 0.1268 | benign | -1.63 | Destabilizing | 0.006 | N | 0.233 | neutral | N | 0.516060146 | None | None | I |
| I/W | 0.9987 | likely_pathogenic | 0.9988 | pathogenic | -2.03 | Highly Destabilizing | 0.998 | D | 0.762 | deleterious | None | None | None | None | I |
| I/Y | 0.9929 | likely_pathogenic | 0.9925 | pathogenic | -1.801 | Destabilizing | 0.978 | D | 0.775 | deleterious | None | None | None | None | I |
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.