Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19155 | 57688;57689;57690 | chr2:178597619;178597618;178597617 | chr2:179462346;179462345;179462344 |
| N2AB | 17514 | 52765;52766;52767 | chr2:178597619;178597618;178597617 | chr2:179462346;179462345;179462344 |
| N2A | 16587 | 49984;49985;49986 | chr2:178597619;178597618;178597617 | chr2:179462346;179462345;179462344 |
| N2B | 10090 | 30493;30494;30495 | chr2:178597619;178597618;178597617 | chr2:179462346;179462345;179462344 |
| Novex-1 | 10215 | 30868;30869;30870 | chr2:178597619;178597618;178597617 | chr2:179462346;179462345;179462344 |
| Novex-2 | 10282 | 31069;31070;31071 | chr2:178597619;178597618;178597617 | chr2:179462346;179462345;179462344 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | rs72646833  |
0.022 | 0.997 | N | 0.545 | 0.26 | None | gnomAD-2.1.1 | 2.04058E-03 | None | None | None | None | I | None | 2.17877E-02 | 7.65567E-04 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 5.49E-05 | 1.12644E-03 |
| R/K | rs72646833 |
0.022 | 0.997 | N | 0.545 | 0.26 | None | gnomAD-3.1.2 | 6.33353E-03 | None | None | None | None | I | None | 2.24277E-02 | 1.37525E-03 | 0 | 0 | 0 | None | 0 | 0 | 1.17675E-04 | 2.06954E-04 | 1.91571E-03 |
| R/K | rs72646833 |
0.022 | 0.997 | N | 0.545 | 0.26 | None | 1000 genomes | 5.39137E-03 | None | None | None | None | I | None | 2.04E-02 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/K | rs72646833 |
0.022 | 0.997 | N | 0.545 | 0.26 | None | gnomAD-4.0.0 | 1.18339E-03 | None | None | None | None | I | None | 2.30976E-02 | 1.11756E-03 | None | 0 | 0 | None | 0 | 6.60939E-04 | 1.86518E-05 | 7.6864E-05 | 1.23318E-03 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9895 | likely_pathogenic | 0.993 | pathogenic | -0.16 | Destabilizing | 0.999 | D | 0.588 | neutral | None | None | None | None | I |
| R/C | 0.9294 | likely_pathogenic | 0.9631 | pathogenic | -0.207 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | I |
| R/D | 0.9956 | likely_pathogenic | 0.9968 | pathogenic | -0.058 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | I |
| R/E | 0.9723 | likely_pathogenic | 0.9794 | pathogenic | 0.014 | Stabilizing | 0.999 | D | 0.641 | neutral | None | None | None | None | I |
| R/F | 0.9945 | likely_pathogenic | 0.997 | pathogenic | -0.288 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| R/G | 0.9814 | likely_pathogenic | 0.9884 | pathogenic | -0.384 | Destabilizing | 1.0 | D | 0.587 | neutral | N | 0.475646475 | None | None | I |
| R/H | 0.8015 | likely_pathogenic | 0.8684 | pathogenic | -0.798 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | I |
| R/I | 0.9734 | likely_pathogenic | 0.9845 | pathogenic | 0.404 | Stabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| R/K | 0.6029 | likely_pathogenic | 0.6862 | pathogenic | -0.209 | Destabilizing | 0.997 | D | 0.545 | neutral | N | 0.503884991 | None | None | I |
| R/L | 0.9515 | likely_pathogenic | 0.9691 | pathogenic | 0.404 | Stabilizing | 1.0 | D | 0.587 | neutral | None | None | None | None | I |
| R/M | 0.9864 | likely_pathogenic | 0.9927 | pathogenic | 0.037 | Stabilizing | 1.0 | D | 0.741 | deleterious | N | 0.47810201 | None | None | I |
| R/N | 0.9943 | likely_pathogenic | 0.9959 | pathogenic | 0.151 | Stabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| R/P | 0.9788 | likely_pathogenic | 0.9838 | pathogenic | 0.237 | Stabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | I |
| R/Q | 0.7782 | likely_pathogenic | 0.8512 | pathogenic | -0.005 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | I |
| R/S | 0.9952 | likely_pathogenic | 0.997 | pathogenic | -0.312 | Destabilizing | 1.0 | D | 0.645 | neutral | N | 0.464339395 | None | None | I |
| R/T | 0.9926 | likely_pathogenic | 0.9954 | pathogenic | -0.097 | Destabilizing | 1.0 | D | 0.643 | neutral | N | 0.471745681 | None | None | I |
| R/V | 0.9828 | likely_pathogenic | 0.9889 | pathogenic | 0.237 | Stabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| R/W | 0.9224 | likely_pathogenic | 0.9593 | pathogenic | -0.23 | Destabilizing | 1.0 | D | 0.795 | deleterious | N | 0.494093124 | None | None | I |
| R/Y | 0.9747 | likely_pathogenic | 0.9863 | pathogenic | 0.149 | Stabilizing | 1.0 | D | 0.732 | prob.delet. | 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.