Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20443 | 61552;61553;61554 | chr2:178590398;178590397;178590396 | chr2:179455125;179455124;179455123 |
| N2AB | 18802 | 56629;56630;56631 | chr2:178590398;178590397;178590396 | chr2:179455125;179455124;179455123 |
| N2A | 17875 | 53848;53849;53850 | chr2:178590398;178590397;178590396 | chr2:179455125;179455124;179455123 |
| N2B | 11378 | 34357;34358;34359 | chr2:178590398;178590397;178590396 | chr2:179455125;179455124;179455123 |
| Novex-1 | 11503 | 34732;34733;34734 | chr2:178590398;178590397;178590396 | chr2:179455125;179455124;179455123 |
| Novex-2 | 11570 | 34933;34934;34935 | chr2:178590398;178590397;178590396 | chr2:179455125;179455124;179455123 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/H | rs781630562  |
-2.694 | 1.0 | D | 0.818 | 0.835 | 0.740584557185 | gnomAD-2.1.1 | 8.31E-06 | None | None | None | None | N | None | 0 | 2.97E-05 | None | 0 | 0 | None | 0 | None | 0 | 9.12E-06 | 0 |
| Y/H | rs781630562 |
-2.694 | 1.0 | D | 0.818 | 0.835 | 0.740584557185 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| Y/H | rs781630562 |
-2.694 | 1.0 | D | 0.818 | 0.835 | 0.740584557185 | gnomAD-4.0.0 | 3.23907E-05 | None | None | None | None | N | None | 1.34009E-05 | 1.68868E-05 | None | 0 | 0 | None | 0 | 0 | 4.08005E-05 | 1.12539E-05 | 1.61015E-05 |
| Y/N | rs781630562 |
None | 1.0 | D | 0.907 | 0.859 | 0.830390191117 | gnomAD-4.0.0 | 1.3761E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80428E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9969 | likely_pathogenic | 0.9939 | pathogenic | -3.188 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| Y/C | 0.9557 | likely_pathogenic | 0.9191 | pathogenic | -1.823 | Destabilizing | 1.0 | D | 0.909 | deleterious | D | 0.655987875 | None | None | N |
| Y/D | 0.9954 | likely_pathogenic | 0.9902 | pathogenic | -3.251 | Highly Destabilizing | 1.0 | D | 0.899 | deleterious | D | 0.672007236 | None | None | N |
| Y/E | 0.9984 | likely_pathogenic | 0.9968 | pathogenic | -3.075 | Highly Destabilizing | 1.0 | D | 0.913 | deleterious | None | None | None | None | N |
| Y/F | 0.3261 | likely_benign | 0.2956 | benign | -1.169 | Destabilizing | 0.999 | D | 0.741 | deleterious | D | 0.62190075 | None | None | N |
| Y/G | 0.989 | likely_pathogenic | 0.9809 | pathogenic | -3.587 | Highly Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | N |
| Y/H | 0.9744 | likely_pathogenic | 0.9583 | pathogenic | -2.018 | Highly Destabilizing | 1.0 | D | 0.818 | deleterious | D | 0.655987875 | None | None | N |
| Y/I | 0.9748 | likely_pathogenic | 0.9557 | pathogenic | -1.869 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| Y/K | 0.9985 | likely_pathogenic | 0.9972 | pathogenic | -2.215 | Highly Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | N |
| Y/L | 0.9641 | likely_pathogenic | 0.9429 | pathogenic | -1.869 | Destabilizing | 0.999 | D | 0.822 | deleterious | None | None | None | None | N |
| Y/M | 0.985 | likely_pathogenic | 0.9741 | pathogenic | -1.522 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| Y/N | 0.9662 | likely_pathogenic | 0.9383 | pathogenic | -2.878 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | D | 0.671805432 | None | None | N |
| Y/P | 0.9994 | likely_pathogenic | 0.9987 | pathogenic | -2.322 | Highly Destabilizing | 1.0 | D | 0.916 | deleterious | None | None | None | None | N |
| Y/Q | 0.9978 | likely_pathogenic | 0.9957 | pathogenic | -2.699 | Highly Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| Y/R | 0.9966 | likely_pathogenic | 0.9942 | pathogenic | -1.831 | Destabilizing | 1.0 | D | 0.916 | deleterious | None | None | None | None | N |
| Y/S | 0.9913 | likely_pathogenic | 0.9829 | pathogenic | -3.27 | Highly Destabilizing | 1.0 | D | 0.91 | deleterious | D | 0.655987875 | None | None | N |
| Y/T | 0.9962 | likely_pathogenic | 0.9919 | pathogenic | -2.984 | Highly Destabilizing | 1.0 | D | 0.913 | deleterious | None | None | None | None | N |
| Y/V | 0.9599 | likely_pathogenic | 0.9311 | pathogenic | -2.322 | Highly Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| Y/W | 0.8432 | likely_pathogenic | 0.8089 | pathogenic | -0.531 | Destabilizing | 1.0 | D | 0.802 | 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.