Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32878 | 98857;98858;98859 | chr2:178539433;178539432;178539431 | chr2:179404160;179404159;179404158 |
| N2AB | 31237 | 93934;93935;93936 | chr2:178539433;178539432;178539431 | chr2:179404160;179404159;179404158 |
| N2A | 30310 | 91153;91154;91155 | chr2:178539433;178539432;178539431 | chr2:179404160;179404159;179404158 |
| N2B | 23813 | 71662;71663;71664 | chr2:178539433;178539432;178539431 | chr2:179404160;179404159;179404158 |
| Novex-1 | 23938 | 72037;72038;72039 | chr2:178539433;178539432;178539431 | chr2:179404160;179404159;179404158 |
| Novex-2 | 24005 | 72238;72239;72240 | chr2:178539433;178539432;178539431 | chr2:179404160;179404159;179404158 |
| 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/R | rs1239539070  |
0.282 | 0.966 | N | 0.643 | 0.346 | None | gnomAD-2.1.1 | 7.13E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 0 |
| I/R | rs1239539070 |
0.282 | 0.966 | N | 0.643 | 0.346 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/R | rs1239539070 |
0.282 | 0.966 | N | 0.643 | 0.346 | None | gnomAD-4.0.0 | 6.81656E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.3236E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5934 | likely_pathogenic | 0.5575 | ambiguous | -0.843 | Destabilizing | 0.525 | D | 0.518 | neutral | None | None | None | None | N |
| I/C | 0.756 | likely_pathogenic | 0.746 | pathogenic | -0.818 | Destabilizing | 0.998 | D | 0.593 | neutral | None | None | None | None | N |
| I/D | 0.8894 | likely_pathogenic | 0.8726 | pathogenic | 0.115 | Stabilizing | 0.974 | D | 0.631 | neutral | None | None | None | None | N |
| I/E | 0.7883 | likely_pathogenic | 0.7671 | pathogenic | 0.049 | Stabilizing | 0.915 | D | 0.618 | neutral | None | None | None | None | N |
| I/F | 0.2771 | likely_benign | 0.251 | benign | -0.814 | Destabilizing | 0.728 | D | 0.544 | neutral | None | None | None | None | N |
| I/G | 0.8303 | likely_pathogenic | 0.8112 | pathogenic | -1.03 | Destabilizing | 0.842 | D | 0.626 | neutral | None | None | None | None | N |
| I/H | 0.7399 | likely_pathogenic | 0.7073 | pathogenic | -0.299 | Destabilizing | 0.974 | D | 0.637 | neutral | None | None | None | None | N |
| I/K | 0.5749 | likely_pathogenic | 0.5366 | ambiguous | -0.225 | Destabilizing | 0.934 | D | 0.62 | neutral | N | 0.496930094 | None | None | N |
| I/L | 0.1741 | likely_benign | 0.1609 | benign | -0.462 | Destabilizing | 0.267 | N | 0.251 | neutral | N | 0.457681059 | None | None | N |
| I/M | 0.172 | likely_benign | 0.1637 | benign | -0.434 | Destabilizing | 0.966 | D | 0.602 | neutral | N | 0.506379083 | None | None | N |
| I/N | 0.4811 | ambiguous | 0.441 | ambiguous | -0.052 | Destabilizing | 0.949 | D | 0.638 | neutral | None | None | None | None | N |
| I/P | 0.8014 | likely_pathogenic | 0.7771 | pathogenic | -0.556 | Destabilizing | 0.974 | D | 0.643 | neutral | None | None | None | None | N |
| I/Q | 0.6483 | likely_pathogenic | 0.6141 | pathogenic | -0.282 | Destabilizing | 0.974 | D | 0.639 | neutral | None | None | None | None | N |
| I/R | 0.4804 | ambiguous | 0.4444 | ambiguous | 0.257 | Stabilizing | 0.966 | D | 0.643 | neutral | N | 0.487465248 | None | None | N |
| I/S | 0.5423 | ambiguous | 0.4949 | ambiguous | -0.659 | Destabilizing | 0.728 | D | 0.578 | neutral | None | None | None | None | N |
| I/T | 0.4539 | ambiguous | 0.4147 | ambiguous | -0.611 | Destabilizing | 0.051 | N | 0.345 | neutral | N | 0.485502379 | None | None | N |
| I/V | 0.1027 | likely_benign | 0.0989 | benign | -0.556 | Destabilizing | 0.005 | N | 0.212 | neutral | N | 0.415469077 | None | None | N |
| I/W | 0.8681 | likely_pathogenic | 0.8596 | pathogenic | -0.769 | Destabilizing | 0.998 | D | 0.64 | neutral | None | None | None | None | N |
| I/Y | 0.657 | likely_pathogenic | 0.6235 | pathogenic | -0.493 | Destabilizing | 0.067 | N | 0.389 | neutral | 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.