Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34204 | 102835;102836;102837 | chr2:178534005;178534004;178534003 | chr2:179398732;179398731;179398730 |
| N2AB | 32563 | 97912;97913;97914 | chr2:178534005;178534004;178534003 | chr2:179398732;179398731;179398730 |
| N2A | 31636 | 95131;95132;95133 | chr2:178534005;178534004;178534003 | chr2:179398732;179398731;179398730 |
| N2B | 25139 | 75640;75641;75642 | chr2:178534005;178534004;178534003 | chr2:179398732;179398731;179398730 |
| Novex-1 | 25264 | 76015;76016;76017 | chr2:178534005;178534004;178534003 | chr2:179398732;179398731;179398730 |
| Novex-2 | 25331 | 76216;76217;76218 | chr2:178534005;178534004;178534003 | chr2:179398732;179398731;179398730 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs2154135586  |
None | 0.989 | N | 0.458 | 0.225 | 0.330589388543 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| D/G | None | None | 0.117 | N | 0.379 | 0.325 | 0.306053231325 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs778105940 |
-1.106 | 0.993 | N | 0.672 | 0.413 | 0.422040124859 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 8.7E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65399E-04 |
| D/N | rs778105940 |
-1.106 | 0.993 | N | 0.672 | 0.413 | 0.422040124859 | gnomAD-4.0.0 | 3.18207E-06 | None | None | None | None | N | None | 0 | 4.57352E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.8591 | likely_pathogenic | 0.8851 | pathogenic | -0.463 | Destabilizing | 0.955 | D | 0.703 | prob.neutral | N | 0.445187056 | None | None | N |
| D/C | 0.9841 | likely_pathogenic | 0.9876 | pathogenic | -0.136 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| D/E | 0.884 | likely_pathogenic | 0.9035 | pathogenic | -0.475 | Destabilizing | 0.989 | D | 0.458 | neutral | N | 0.451592954 | None | None | N |
| D/F | 0.9902 | likely_pathogenic | 0.9932 | pathogenic | 0.161 | Stabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| D/G | 0.8732 | likely_pathogenic | 0.8897 | pathogenic | -0.835 | Destabilizing | 0.117 | N | 0.379 | neutral | N | 0.479147701 | None | None | N |
| D/H | 0.9372 | likely_pathogenic | 0.953 | pathogenic | -0.027 | Destabilizing | 1.0 | D | 0.809 | deleterious | N | 0.491315097 | None | None | N |
| D/I | 0.983 | likely_pathogenic | 0.988 | pathogenic | 0.523 | Stabilizing | 0.999 | D | 0.862 | deleterious | None | None | None | None | N |
| D/K | 0.9738 | likely_pathogenic | 0.9817 | pathogenic | -0.112 | Destabilizing | 0.998 | D | 0.84 | deleterious | None | None | None | None | N |
| D/L | 0.9821 | likely_pathogenic | 0.9869 | pathogenic | 0.523 | Stabilizing | 0.998 | D | 0.839 | deleterious | None | None | None | None | N |
| D/M | 0.9931 | likely_pathogenic | 0.9944 | pathogenic | 0.875 | Stabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| D/N | 0.5905 | likely_pathogenic | 0.6241 | pathogenic | -0.733 | Destabilizing | 0.993 | D | 0.672 | neutral | N | 0.501773845 | None | None | N |
| D/P | 0.9964 | likely_pathogenic | 0.9975 | pathogenic | 0.22 | Stabilizing | 0.999 | D | 0.847 | deleterious | None | None | None | None | N |
| D/Q | 0.9661 | likely_pathogenic | 0.9739 | pathogenic | -0.56 | Destabilizing | 0.999 | D | 0.725 | prob.delet. | None | None | None | None | N |
| D/R | 0.9673 | likely_pathogenic | 0.9763 | pathogenic | 0.109 | Stabilizing | 0.998 | D | 0.855 | deleterious | None | None | None | None | N |
| D/S | 0.6612 | likely_pathogenic | 0.6876 | pathogenic | -0.965 | Destabilizing | 0.983 | D | 0.593 | neutral | None | None | None | None | N |
| D/T | 0.9128 | likely_pathogenic | 0.9214 | pathogenic | -0.648 | Destabilizing | 0.998 | D | 0.839 | deleterious | None | None | None | None | N |
| D/V | 0.9465 | likely_pathogenic | 0.9591 | pathogenic | 0.22 | Stabilizing | 0.997 | D | 0.841 | deleterious | N | 0.494058439 | None | None | N |
| D/W | 0.9972 | likely_pathogenic | 0.9979 | pathogenic | 0.416 | Stabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| D/Y | 0.9145 | likely_pathogenic | 0.9392 | pathogenic | 0.44 | Stabilizing | 1.0 | D | 0.848 | deleterious | N | 0.481726647 | 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.